BMC Cancer[JOURNAL]
Sun
200 papers
Sanguinarine as a multi-target therapeutic candidate for laryngeal cancer: insights from network pharmacology, molecular dynamics and in vitro validation.
Luo M, Zhu D, Yin X
BMC Cancer · 2026 Jun · PMID 42323571 · Full text
OBJECTIVE: To identify the core targets and elucidate the potential molecular mechanisms of sanguinarine (SA) against laryngeal squamous cell carcinoma (LSCC), and to validate its antitumor effects in vitro. METHODS: Pot...
OBJECTIVE: To identify the core targets and elucidate the potential molecular mechanisms of sanguinarine (SA) against laryngeal squamous cell carcinoma (LSCC), and to validate its antitumor effects in vitro. METHODS: Potential targets of SA were predicted using SwissTargetPrediction, TargetNet, and SuperPred and intersected with LSCC-related targets obtained from the GeneCards, OMIM, and DISEASES databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed using the STRING database (combined score > 0.900), and topological parameters including degree centrality (DC), betweenness centrality (BC), closeness centrality (CC), eigenvector centrality (EC), and local average connectivity (LAC) were calculated in Cytoscape to identify core genes based on median thresholds. Molecular docking and 100-ns molecular dynamics (MD) simulations were conducted for epidermal growth factor receptor (EGFR), Phosphatidylinositide-3-kinase catalytic subunit alpha (PIK3CA), phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit β (PIK3CB), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), and Non-Receptor Tyrosine Kinase (SRC). The effects of SA on LSCC were evaluated using CCK-8, colony formation, Transwell migration, and wound-healing assays in TU177 cells and TU212. RESULTS: A total of 213 common targets were identified, which were significantly enriched in PI3K-Akt signaling, EGFR tyrosine kinase inhibitor resistance, and adhesion- and migration-related pathways. The PPI network comprised 259 nodes and 259 edges, from which five core genes-PIK3CA, PIK3CB, PIK3CD, EGFR, and SRC-were identified. Molecular docking revealed strong binding affinities between SA and the PI3K family proteins (- 9.79 to - 10.96 kcal/mol), as well as EGFR (- 8.58 kcal/mol) and SRC (- 6.77 kcal/mol). MD simulations indicated greater stability of SA complexes with EGFR and PI3K family members compared with SRC. In vitro assays demonstrated that SA significantly inhibited TU177 cell and TU212 cell proliferation, colony formation, and migration. CONCLUSION: SA may exert anti-laryngeal cancer effects through synergistic multi-target inhibition centered on the EGFR/SRC/PI3K signaling axis, highlighting its potential as a promising therapeutic candidate for LSCC.
Radiomics analysis of CT imaging for predicting MIT family translocation renal cell carcinoma: a multicenter retrospective clinical study.
Lin SW, Wu XH, Liu WQ … +8 more , Chen DN, Lin Y, Liu ZS, Wang JY, Yin HB, Xue XY, Xu N, Chen SH
BMC Cancer · 2026 Jun · PMID 42323535 · Full text
OBJECTIVE: This study aimed to investigate the imaging characteristics of Microphthalmia Transcription Factor (MIT) Family Translocation Renal Cell Carcinoma (MIT-RCC), assess the relationship between CT-based radiomics...
OBJECTIVE: This study aimed to investigate the imaging characteristics of Microphthalmia Transcription Factor (MIT) Family Translocation Renal Cell Carcinoma (MIT-RCC), assess the relationship between CT-based radiomics and MIT-RCC, and develop a predictive model to improve preoperative non-invasive diagnosis. MATERIALS AND METHODS: A retrospective analysis was conducted using preoperative computed tomography (CT) images and clinical data from 746 RCC patients (77 MIT-RCC and 669 other RCC subtypes) across multiple centers. Regions of interest (ROIs) in both tumor and normal renal parenchymal during non-contrast and arterial phases were manually segmented using ITK-SNAP. Radiomics features were extracted via Python, and the Least Absolute Shrinkage and Selection Operator (LASSO) method was applied for feature selection. A combined model incorporating radiomics scores and clinical predictors (age, stage) was developed using logistic regression and visualized as a nomogram. Patients from two centers formed the training cohort (n = 539), and three other centers served as the validation cohort (n = 207). RESULTS: From 1316 features per ROI, 22 tumor and 24 normal renal parenchymal features were selected. The nomogram integrating Tumor_Radscores, Kidney_Radscores, age, and clinical stage showed strong predictive performance in the training cohort (area under the curve [AUC] = 0.952, 95% confidence interval [CI]: 0.927-0.971) and validation cohort (AUC = 0.914, 95% CI: 0.879-0.942), with good calibration and clinical utility. CONCLUSION: By integrating radiomics and clinical data, the proposed nomogram achieved accurate, non-invasive prediction of MIT-RCC, offering valuable support for preoperative diagnosis and personalized treatment planning.
Thiostrepton potentiates chemotherapy-induced cell death in cisplatin-resistant SKOV3 cells.
Motafeghi F, Barghi EG, Gharab JG … +4 more , Mortazavi P, Tehrani FR, Ashari S, Barghi NG
BMC Cancer · 2026 Jun · PMID 42323534 · Full text
BACKGROUND: One of the main problems in the treatment of ovarian cancer is resistance to the main drug (cisplatin). Thiostrepton (TST), a thiazole antibiotic, helps weaken cancer cells and enhance the efficacy of platinu...
BACKGROUND: One of the main problems in the treatment of ovarian cancer is resistance to the main drug (cisplatin). Thiostrepton (TST), a thiazole antibiotic, helps weaken cancer cells and enhance the efficacy of platinum-based therapy. This study examines the combination of TST and cisplatin in the SKOV3/CDDP model of resistance, focusing on associated changes in oxidative stress, mitochondrial function, genotoxicity, apoptosis, inflammatory mediators, and Wnt/β-catenin output. METHODS: SKOV3/CDDP cells were treated with cisplatin at an IC50 concentration, TST at concentrations (1, 2.5, 5 µM), and the combination of these two substances for 24 h. Cell viability, intracellular energy, and membrane damage were measured by MTT and ATP assays and LDH release, respectively. Apoptosis was assessed using caspase-3/7 and TUNEL activity.DNA damage was analyzed using the Comet and CBMN assays. Oxidative stress and antioxidant defense were assessed by measuring ROS, MDA, GSH/GSSG ratio, and SOD, catalase, and GPx activities. Mitochondrial dysfunction (ΔΨm, NAD+/NADH), cytokines (IL-6, IL-8, TNF-α, IL-1β), and Wnt/β-catenin target genes (c-MYC, AXIN2) were evaluated. RESULTS: The combination of cisplatin and TST was much more potent than when either was used alone. This combination increased oxidative stress processes, increased DNA damage, and decreased antioxidant capacity in cancer cells. Inflammatory cytokine levels were also increased, and c-MYC and AXIN2 expression were reduced, which was accompanied by the attenuation of β-catenin-dependent transcription. CONCLUSION: Overall, TST increased the sensitivity of resistant ovarian cancer cells to cisplatin. Its anticancer effect was enhanced by oxidative-mitochondrial stress and DNA damage pathways, along with reduced Wnt/β-catenin transcription.
Prognostic value of combined FIB-4 and AFP in predicting survival after hepatectomy for hepatocellular carcinoma: a multicenter cohort study.
Yang Y, Yang H, Du Y … +3 more , Hou S, Zhang K, Xiao Z
BMC Cancer · 2026 Jun · PMID 42323530 · Full text
BACKGROUND: Accurate prognostic assessment remains challenging in patients with hepatocellular carcinoma (HCC). Although the fibrosis-4 (FIB-4) index is widely used for non-invasive evaluation of liver fibrosis, its prog...
BACKGROUND: Accurate prognostic assessment remains challenging in patients with hepatocellular carcinoma (HCC). Although the fibrosis-4 (FIB-4) index is widely used for non-invasive evaluation of liver fibrosis, its prognostic value in HCC remains uncertain. This study evaluates the prognostic utility of the FIB-4 index, alpha-fetoprotein (AFP), and the combined AFP-FIB-4 score for long-term survival in patients with HCC following hepatectomy. METHODS: A retrospective analysis was conducted on 1174 HCC patients who underwent hepatectomy at the First People's Hospital of Changde City and Guangxi Medical University Cancer Hospital between 2014 and 2024. Survival analysis, Cox regression, and receiver operating characteristic (ROC) curve analysis were employed to assess the predictive performance of the FIB-4 index, AFP, and the combined AFP-FIB-4 score for long-term survival. RESULTS: Multivariate Cox regression analysis demonstrated that the FIB-4 index was not an independent predictor of disease-free survival (DFS) or overall survival (OS) in HCC patients. In contrast, AFP emerged as an independent risk factor for both DFS (HR = 1.391, 95%CI = 1.193-1.623, P < 0.001) and OS (HR = 1.267, 95%CI = 1.080-1.486, P = 0.004). Notably, the combined AFP-FIB-4 score served as a stronger independent prognostic factor for both DFS (HR = 1.404, 95% CI = 1.204-1.638, P < 0.001) and OS (HR = 1.378, 95%CI = 1.196-1.588, P < 0.001). Subgroup analysis revealed that the FIB-4 index alone failed to significantly predict prognosis in patients with Barcelona Clinic Liver Cancer (BCLC) stage B or C (P > 0.05), while AFP was ineffective in distinguishing prognosis in patients with BCLC stage 0 or A (P > 0.05). However, the AFP-FIB-4 score successfully stratified each BCLC stage subgroup into two groups with significantly different prognoses (all P < 0.05). ROC analysis demonstrated that the AFP-FIB-4 score achieved a significantly higher area under the curve (AUC 0.623) compared with AFP (AUC 0.553) and the FIB-4 index (AUC 0.565). CONCLUSION: Incorporating AFP into the FIB-4 index enhances its prognostic performance. The AFP-FIB-4 score serves as a robust predictor of DFS and OS in HCC patients undergoing hepatectomy across different BCLC stages.
PD-L1 copy number loss is associated with lower survival in women with advanced breast cancer in Indonesian cohort.
Karsono R, Al Azhar M, Utari AD … +2 more , Perdana AB, Umaya ER
BMC Cancer · 2026 Jun · PMID 42321710 · Full text
BACKGROUND: The prognostic value of PD-L1 copy number variation (CNV) in advanced breast cancer (BC) patients remains unclear. This study investigated the association between PD-L1 CNV and its prognostic significance in...
BACKGROUND: The prognostic value of PD-L1 copy number variation (CNV) in advanced breast cancer (BC) patients remains unclear. This study investigated the association between PD-L1 CNV and its prognostic significance in advanced BC. METHODS: PD-L1 CNV was analyzed using real-time PCR in advanced BC patients (n = 132) who received chemotherapy or hormonal therapy, along with a non-malignant control group (n = 5) obtained from patients with histopathologically confirmed fibroadenoma used as reference controls. The association of PD-L1 CNV with overall survival and clinicopathological features was determined. RESULTS: PD-L1 CNVs were identified in 22% (29/132) of advanced BC cases, comprising 9 CN losses and 20 CN gains. PDL-1 CN loss was associated with low overall survival (OS) (HR = 2.61; 95% CI = 1.10-6.21; p = 0.024) and remained significant after multivariate adjustment (HR = 3.13; 95% CI = 1.23-7.94; p = 0.016). The adverse prognostic effect was pronounced in HR-positive (p = 0.004) and HER2-negative patients (p = 0.040). PD-L1 CNVs were more frequent in patients > 40 years (p = 0.027) and HER2-negative tumors (p = 0.019). CONCLUSIONS: PD-L1 CN loss was associated with lower OS, particularly in HR(+) and HER2(-) patients. This result revealed the prognostic value of PD-L1 CNV in Indonesian advanced BC who received primary systemic therapy.
Prognostic outcomes of adjuvant chemotherapy in postoperative patients with cancer undergoing hemodialysis versus non-hemodialysis patients: a retrospective nationwide cohort study.
Ishii T, Watanabe T, Ichinose Y … +2 more , Mano H, Higashi T
BMC Cancer · 2026 Jun · PMID 42321691 · Full text
BACKGROUND: Survival outcomes for patients with cancer undergoing hemodialysis (HD) are poorer than those for patients not undergoing HD, possibly owing to altered chemotherapy protocols or undertreatment to address rena...
BACKGROUND: Survival outcomes for patients with cancer undergoing hemodialysis (HD) are poorer than those for patients not undergoing HD, possibly owing to altered chemotherapy protocols or undertreatment to address renal impairment and drug toxicity concerns. Adjuvant chemotherapy should be administered appropriately with evidence-based drug selection. However, in patients undergoing HD, the administration of adjuvant chemotherapy and its association with prognosis remain unclear. We evaluated the association between adjuvant chemotherapy and survival outcomes in patients undergoing HD compared with those not undergoing HD in Japan. METHODS: A nationwide dataset combining Hospital-Based Cancer Registry and Diagnosis Procedure Combination survey data was utilized. The study included adult patients newly diagnosed with colorectal, gastric, breast, or non-small cell lung cancer between January 2013 and December 2015. The primary survival analysis used a 90-day landmark approach: patients who were alive at postoperative day 90 and had survival follow-up information available thereafter were included, adjuvant chemotherapy was defined as treatment initiated within 90 days after surgery, and overall survival was measured from postoperative day 90 to death or last confirmed survival. Multivariable Cox regression models included hemodialysis status, adjuvant chemotherapy, their interaction term, age, sex, cancer type, Barthel Index, comorbidities, and hospital type. RESULTS: In the final cohort, 44,281 patients met the eligibility criteria. Among 43,984 patients included in the primary 90-day landmark analysis, 451 were undergoing HD. Patients undergoing HD were less likely to initiate adjuvant chemotherapy within 90 days after surgery than those not undergoing HD (30.4% vs. 68.0%, P < 0.001). In the multivariable Cox model with an interaction term, HD was associated with worse overall survival among patients who did not initiate adjuvant chemotherapy within 90 days after surgery (adjusted hazard ratio [aHR], 1.91; 95% confidence interval [CI], 1.67-2.18; P < 0.001), and the HD × adjuvant chemotherapy interaction was statistically significant (P = 0.002). The association between adjuvant chemotherapy and overall survival was evident among patients not undergoing HD but was not statistically significant among patients undergoing HD. In an exploratory analysis restricted to patients undergoing HD who initiated adjuvant chemotherapy, use of a standard regimen was associated with better survival than use of a non-standard regimen. CONCLUSIONS: Patients undergoing HD were less likely to receive adjuvant chemotherapy and had worse overall survival. The association between adjuvant chemotherapy and survival appeared attenuated among patients undergoing HD. Further prospective studies are needed to define optimal postoperative chemotherapy strategies for this population.
Dissecting T-cell exhaustion heterogeneity and immune ecosystem dynamics in colorectal cancer through multi-omics machine learning.
Zhang Z, Ouyang P, Cui K … +9 more , Lai J, Wen Y, Deng X, Chen W, Xian Z, Qi Q, Bao Z, Gong J, He X
BMC Cancer · 2026 Jun · PMID 42321664 · Full text
BACKGROUND: Immunotherapy has shown limited efficacy in a substantial subset of CRC patients, yet the mechanisms underlying therapeutic resistance remain incompletely understood. T-cell exhaustion (TEX) in the tumor micr...
BACKGROUND: Immunotherapy has shown limited efficacy in a substantial subset of CRC patients, yet the mechanisms underlying therapeutic resistance remain incompletely understood. T-cell exhaustion (TEX) in the tumor microenvironment has been identified as a pivotal driver of immune evasion and tumor progression. Dissecting its contribution to CRC is essential for the development of rational therapeutic strategies. METHODS: We integrated scRNA-seq and bulk transcriptomic data to identify CD8⁺ T-cell exhaustion core genes via hdWGCNA and ten machine learning algorithms, constructed a multivariate Cox-based TEX score model validated across independent cohorts and immunotherapy datasets, and experimentally confirmed our findings by RT-qPCR, Western blot, and quantitative multiplex immunofluorescence in clinical CRC specimens. RESULTS: Our single-cell analysis revealed a continuum of intra-tumoral CD8⁺ T-cell exhaustion states, identified a five-gene TEX score (KLF3, LMNA, SLC2A3, ARL4C, TIMP1) that predicted poor prognosis and an immunosuppressive microenvironment. Further experimental validation confirmed the differential expression and spatial co-localization with CD8⁺ T cells in clinical specimens. CONCLUSIONS: Our findings implicate TEX as a central mediator of immunotherapy resistance in CRC, offering a clinically actionable framework for patient stratification and therapeutic decision-making.
ELF-3 and TSC-1 as potential markers of recurrence in low-risk non-muscle-invasive bladder cancer.
Altın E, Doğan Ç, Arslan Aİ … +5 more , Topkaç EC, Yazıcı CM, Özcan R, Akgül HM, Şahin MF
BMC Cancer · 2026 Jun · PMID 42321663 · Full text
OBJECTIVE: Tumor recurrence is a major clinical challenge in low-risk non-muscle invasive bladder cancer (NMIBC). Molecular studies have identified two main subtypes with distinct genetic pathways: papillary, low-grade t...
OBJECTIVE: Tumor recurrence is a major clinical challenge in low-risk non-muscle invasive bladder cancer (NMIBC). Molecular studies have identified two main subtypes with distinct genetic pathways: papillary, low-grade tumors, often with FGFR3 mutations and favorable outcomes, and nonpapillary, high-grade tumors, which are linked to higher rates of progression and muscle invasion. This study evaluates the prognostic value of immunohistochemical (IHC) markers- cluster of differentiation 44 (CD44), cytokeratin 5/6 (CK5/6), cytokeratin 20 (CK20), GATA-binding protein 3 (GATA3), human epidermal growth factor receptor 2 (Cerb-B2), E74-like factor 3 (ELF-3), and tuberous sclerosis complex 1 (TSC-1)-for recurrence in patients with low-risk NMIBC. MATERIALS AND METHODS: This retrospective study evaluated 40 patients with NMIBC selected from 320 individuals who underwent transurethral resection of bladder tumors (TUR-BT) between 2011 and 2019. Patients were categorized into two groups: recurrence (n = 20), defined as tumor recurrence following TUR-BT, and nonrecurrence (n = 20), those with no recurrence during follow-up. Tissues were reevaluated and stained for the following markers using IHC methods: CK5/6, CK20, CD44, GATA3, Cerb-B2, ELF-3, and TSC-1. Statistical analysis was performed to assess associations between clinicopathological variables and recurrence. RESULTS: Recurrence was significantly correlated with tumor number (p = 0.036), whereas age, sex, smoking status, and tumor size showed no significant association (p > 0.05). CD44 positivity was predominantly observed in nonrecurrent cases (p = 0.022), whereas TSC-1 positivity was strongly associated with recurrence (p = 0.003). ELF-3 expression was uniformly positive in all cases and did not predict recurrence. Multivariate regression revealed that CD44 positivity reduced the recurrence risk (OR = 0.142, 95% CI: [0.028-0.714]), while TSC-1 positivity increased it more than 21-fold (OR = 21.871, 95% CI: [2.125-115.15]). Tumors located at the ureteral orifice were associated with increased recurrence risk (OR = 10.231, 95% CI: [1.121-93.341]). CONCLUSION: This study suggests that low CD44 expression and high TSC-1 expression in patients with low-risk NMIBC may serve as prognostic markers for tumor recurrence. Assessing these markers can facilitate earlier identification of at-risk patients, enabling strict surveillance and timely management of treatment strategies.
Exploring the immune landscape and immunotherapy relevance of ER stress-related lncRNAs in melanoma through multi-omics and explainable machine learning.
Hu B, Shi C, Qi M … +2 more , Ding A, Zhang J
BMC Cancer · 2026 Jun · PMID 42321658 · Full text
BACKGROUND: Melanoma is a highly aggressive malignancy with poor clinical outcomes, and endoplasmic reticulum (ER) stress plays an important role in tumor progression, immune regulation, and therapeutic resistance. Howev...
BACKGROUND: Melanoma is a highly aggressive malignancy with poor clinical outcomes, and endoplasmic reticulum (ER) stress plays an important role in tumor progression, immune regulation, and therapeutic resistance. However, the prognostic significance and biological functions of ER stress-related long noncoding RNAs (ERlncRNAs) in melanoma remain largely unclear. METHODS: We performed an integrative analysis to systematically investigate the prognostic significance and biological relevance of ERlncRNAs in melanoma by combining bulk transcriptomic analysis, single-cell RNA sequencing, explainable machine learning, and experimental validation. Transcriptomic and clinical data were obtained from the TCGA, GTEx, and GEO databases. A 13-ERlncRNA prognostic signature was established and externally validated. Survival analysis, receiver operating characteristic analysis, and nomogram evaluation were conducted to assess model performance. SHapley Additive exPlanations (SHAP) analysis was incorporated to improve the interpretability of ERlncRNA-based risk-group classification. Immune infiltration, tumor mutational burden, TIDE scores, immune checkpoint gene expression, and predicted sensitivity to selected small-molecule targeted agents were further analyzed. Functional experiments were performed to evaluate the roles of selected ERlncRNAs in melanoma cell proliferation, colony formation, migration, and apoptosis, and Western blot analysis was used to assess the expression of ER stress-related proteins following gene silencing. RESULTS: A 13-ERlncRNA signature with stable prognostic performance was established and externally validated in melanoma cohorts. The model effectively stratified patients into high- and low-risk groups with significantly different overall survival and served as an independent prognostic predictor. SHAP analysis identified major contributors to ERlncRNA-based risk-group classification and improved model interpretability. Significant differences in immune cell infiltration, tumor mutational burden, TIDE scores, immune checkpoint gene expression, and predicted sensitivity to selected small-molecule targeted agents were observed between the two risk groups. Single-cell RNA sequencing further revealed marked heterogeneity and dynamic alterations of ER stress-related features across distinct cell populations in melanoma. Functional experiments showed that knockdown of representative ERlncRNAs inhibited melanoma cell proliferation, colony formation, and migration, while promoting apoptosis. Moreover, gene silencing was accompanied by increased CHOP expression without an obvious concomitant increase in GRP78, suggesting a shift of the ER stress response toward a pro-apoptotic state in melanoma cells. CONCLUSIONS: This study established an interpretable ERlncRNA-based prognostic framework for melanoma and highlighted the biological and clinical relevance of ER stress-related lncRNAs. These findings provide insights into tumor heterogeneity, immune-related characteristics, and potential therapeutic stratification in melanoma, and suggest that selected ERlncRNAs may contribute to melanoma progression partly through modulation of ER stress-associated apoptotic signaling.
NAV-005, a high-affinity MUC16/CA125 antagonist for the treatment of humoral immunosuppressed cancers.
Nicolaides NC, Kline JB, Grasso L
BMC Cancer · 2026 Jun · PMID 42321642 · Full text
OBJECTIVE: This study aimed to develop a high-affinity therapeutic antagonist to overcome tumor-produced MUC16/CA125 (herein CA125) mediated immunosuppression of anticancer therapeutic antibodies and antibody-drug conjug...
OBJECTIVE: This study aimed to develop a high-affinity therapeutic antagonist to overcome tumor-produced MUC16/CA125 (herein CA125) mediated immunosuppression of anticancer therapeutic antibodies and antibody-drug conjugates (ADCs). The goal was to generate an antagonist that blocks CA125 binding to IgG1 antibodies, restores antibody interaction with CD16a Fc-γ-activating receptors (herein CD16a) and C1q protein, and re-enables maximal antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against cancer cells. Since CA125 binding to ADCs impairs its cytotoxicity by reducing ADC internalization, the antagonist was further designed to restore maximal ADC activity. Achieving these aims supports the clinical development of CA125 antagonists for treating cancers marked by humoral immunosuppression. METHODS: Human IgG1 Fc fusion proteins with varying mesothelin binding domain (MBD) motifs were engineered and tested for high-affinity CA125 binding. Antagonist efficacy was assessed by measuring restoration of CD16a and C1q binding to IgG1 antibodies suppressed by CA125. ADC internalization assays evaluated the effect of CA125 and antagonists on ADC uptake. Cellular assays, including Jurkat-CD16a reporter and PBMC-based ADCC assays, measured restoration of antibody-CD16a mediated immune effector cell killing of target cells. Cytotoxicity assays assessed CDC and ADC mediated cell killing. RESULTS: NAV-005 (MBD2-Fc), a lead antagonist, bound CA125 with high affinity and blocked its binding to IgG1-type antibodies. NAV-005 reversed CA125-induced antibody immunosuppression, thereby restoring IgG1 mediated ADCC and CDC by preventing CA125-IgG1 interaction. NAV-005 also prevented CA125-ADC cell surface interactions, thereby restoring maximal ADC internalization and target cell killing. CONCLUSION: Tumor-produced CA125 impairs therapeutic antibody and ADC efficacy via humoral immunosuppression. NAV-005 counteracts this effect, restoring antitumor activity of antibodies and ADCs in CA125-expressing cancers. These results support the continued development of CA125 antagonists as adjuncts to antibody-based cancer therapies.
Immunohistochemical breast cancer subtypes in Palestinian Women: an 18-year multicenter retrospective analysis.
Salhi I, Maqboul H, Jallad F … +4 more , Jaradat H, Bannoura S, El-Krunz D, Karmi B
BMC Cancer · 2026 Jun · PMID 42316123 · Full text
OBJECTIVE: To describe the demographic, geographic, and immunohistochemical (IHC) subtype distribution of breast cancer in a large multi-center Palestinian cohort, and to examine temporal trends in subtype frequency over...
OBJECTIVE: To describe the demographic, geographic, and immunohistochemical (IHC) subtype distribution of breast cancer in a large multi-center Palestinian cohort, and to examine temporal trends in subtype frequency over an 18-year period. METHODS: A retrospective descriptive analysis of 2,323 consecutive female breast cancer patients diagnosed at 27 pathology service centers across 11 Palestinian governorates between August 2008 and May 2026. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status were abstracted from the immunohistochemistry reports. Patients with complete ER, PR, and HER2 data were classified into four molecular surrogate subtypes: Luminal A-like (HR+/HER2-), Luminal B HER2+ (HR+/HER2+), HER2-enriched (HR-/HER2+), and triple-negative (HR-/HER2-). RESULTS: The cohort was geographically broad, with the highest proportions of specimens contributed from Nablus (51.5%) and Ramallah & Al-Bireh (20.9%) governorates. Mean age at diagnosis was 52.8 years (SD 13.2; range 19-98). Among patients with reported IHC results, ER positivity was 67.4% (1,352/2,005), PR positivity was 63.4% (1,166/1,840), and HER2 positivity was 21.4% (425/1,985). Of the 1,628 patients with complete triple-marker data, Luminal A-like tumors comprised the majority (60.7%, n = 988), followed by triple-negative (17.6%, n = 286), Luminal B HER2+ (11.9%, n = 193), and HER2-enriched (9.9%, n = 161). HER2-enriched tumors occurred in younger patients (mean age 48.8 years) than the other subtypes. CONCLUSION: Palestinian breast cancer is dominated by hormone-receptor-positive disease, but the combined HER2-positive fraction (21.8%) and triple-negative fraction (17.6%) together account for nearly two-fifths of cases - a higher burden of aggressive subtypes than is reported in most Western series. These findings underline the importance of universal IHC testing and targeted therapy access in Palestinian breast cancer care.
Impact of precision oncology research in pediatric poor prognosis cancer: patient, parent and healthcare provider perspectives.
McCloskey N, Mahon P, Rassekh SR … +5 more , Hetherington K, Regier DA, Wakefield CE, Pollard S, Deyell RJ
BMC Cancer · 2026 Jun · PMID 42316091 · Full text
BACKGROUND: Comprehensive genomic analyses are increasingly accessible to children, adolescents and young adults (AYAs) with poor prognosis cancers. Challenges and successes of pediatric precision oncology studies from t...
BACKGROUND: Comprehensive genomic analyses are increasingly accessible to children, adolescents and young adults (AYAs) with poor prognosis cancers. Challenges and successes of pediatric precision oncology studies from the perspectives of AYA patients, parents and healthcare providers (HCPs) are poorly described. METHODS: Between March 2021 and May 2023, we interviewed AYA patients (12-21 years), parents and HCPs who participated in pediatric precision oncology studies for poor prognosis cancers in British Columbia. Interviews followed an investigator-developed semi-structured topic guide. Data were coded inductively and deductively by one qualitative researcher and one trainee, supported by two additional team members. Analytic themes were established using qualitative thematic analysis. RESULTS: We interviewed 9 AYAs, 10 parents, and 17 HCPs. We identified five analytic themes: importance of clear communication of study information between patients, families and multidisciplinary HCPs; a need to support disclosure, understanding and clinical integration of research results; barriers to accessing innovative therapy and mitigation strategies; approaches to managing parent, patient and HCP hopes and expectations; personal challenges and stressors related to participation. CONCLUSIONS: We highlight unmet needs and offer practical considerations for integrating precision oncology into clinical practice. Considerations include educating and supporting oncologists through genomics results disclosure, increasing engagement with multidisciplinary HCPs, streamlining access to study information and results, coordinating efforts to clinically validate results and access therapies, and establishing real-world outcome data to inform clinical decision-making. Implementation of these strategies will optimize care for patients and families who are navigating poor prognosis cancers.
Screening of cytochrome CYP26A1 expression in different bone tumors.
Al-Zu'bi B, Alshammari FOFO, AlQaisi R … +5 more , Al-Abadleh AA, Satari AO, Al-Sarayreh S, Al-Saraireh YM, Hareedy MS
BMC Cancer · 2026 Jun · PMID 42316073 · Full text
BACKGROUND: Cytochrome P450 26A1 (CYP26A1) is a retinoic acid metabolizing enzyme which is overexpressed in many cancers. However, its expression in bone tumors has not been characterized. METHODS: Immunohistochemistry w...
BACKGROUND: Cytochrome P450 26A1 (CYP26A1) is a retinoic acid metabolizing enzyme which is overexpressed in many cancers. However, its expression in bone tumors has not been characterized. METHODS: Immunohistochemistry was used to evaluate CYP26A1 expression in a human bone disease spectrum comprising duplicated cores of 95 cases of benign, intermediate and malignant bone tumors alongside normal bone samples. STRING database was utilized to perform CYP26A1 protein-protein interaction and functional enrichment analyses. RESULTS: CYP26A1 staining was not identified in the normal bone samples analyzed. Collectively, CYP26A1 was expressed in 31.6% (30/95) of bone tumors, with cytoplasmic localization, while no immunoreactivity was detected in normal tissues. Compared with benign (18.8%) and malignant tumors (27.1%), intermediate bone tumors expressed CYP26A1 significantly more frequently (66.7%). This difference in expression between tumor categories was statistically confirmed (p < 0.05, Cramér's V = 0.382). Among intermediate tumors, CYP26A1 was detected with high frequency and weak staining intensity in giant cell tumors (GCTs, 14/20 cases), with immunoreactivity localized mainly in osteoblast-like and osteocyte-like stromal cells. Malignant bone tumors predominantly showed focal or an absence of CYP26A1 immunoreactivity. However, strong CYP26A1 immunoreactivity was displayed in the limited chordoma and adamantinoma cases examined, while osteosarcoma and Ewing sarcoma displayed no immunoreactivity in general. Interestingly, functional enrichment analysis confirmed the established association of CYP26A1 with retinoid metabolic pathways. CONCLUSIONS: CYP26A1 expression was most frequent in giant cell tumors of bone. While also detected in a subset of other bone tumors, expression was limited or absent in most benign and malignant lesions, and entirely absent in normal bone tissue. These findings provide novel descriptive insight into CYP26A1 distribution and support further investigation into its role in retinoid-related pathways in bone tumor biology.
Real-world evidence for the impact of circadian clock on the benefit from immune checkpoint inhibitors in solid tumors.
Soyfer EM, Lee BJ, Qavi AJ … +3 more , Masri S, Fleischman AG, Dayyani F
BMC Cancer · 2026 Jun · PMID 42316066 · Full text
BACKGROUND: The circadian clock regulates tumor-immune interactions in a time-of-day-dependent manner, yet whether this translates to a clinically meaningful benefit across diverse solid tumors in real-world populations...
BACKGROUND: The circadian clock regulates tumor-immune interactions in a time-of-day-dependent manner, yet whether this translates to a clinically meaningful benefit across diverse solid tumors in real-world populations remains unclear. METHODS: We retrospectively analyzed 969 patients receiving anti-PD-1 or anti-PD-L1 therapy at UCI Health between 2018 and 2022. Patients were classified as early (before 12 PM) or late (12 PM or after) based on infusion time. The primary outcome was disease control rate (DCR), defined as complete response (CR), partial response (PR), or stable disease (SD) per RECIST criteria. Unadjusted comparisons used the Pearson chi-square test. Multivariable logistic regression adjusting for disease stage, age, and ethnicity was performed in 806 patients with complete covariate data. Propensity score-matched analyses and sensitivity analyses using alternative exposure definitions were conducted. RESULTS: Early infusion was associated with significantly higher DCR compared with late infusion (49% vs. 40%, p = 0.007). This association persisted after multivariable adjustment (adjusted OR 1.18, 95% CI 1.02-1.38, p = 0.024). The effect was directionally consistent across subgroups defined by sex, age, stage, and ICI agent. In ethnicity-stratified analyses, the association was significant among non-Hispanic patients (adjusted OR 1.18, 95% CI 1.02-1.39) but was indeterminate among Hispanic patients due to limited sample size (adjusted OR 1.18, 95% CI 0.84-1.65); the ethnicity-by-TOD interaction term was non-significant (p = 0.958). Sensitivity analyses using alternative exposure definitions and propensity score matching yielded consistent results. CONCLUSIONS: In a large, heterogeneous real-world cohort spanning multiple tumor types and a diverse patient population, early ICI administration was independently associated with higher DCR. These findings support a chronotherapeutic effect of ICI timing and underscore DCR as a sensitive endpoint for its detection. Prospective validation across tumor types and demographic subgroups is warranted.
Effect of immunonutrition on surgery outcomes in cancer patients: evidence from an umbrella review on interventional and observational meta-analyses.
Mardani H, Riazi Khameneh U, Jafari A … +13 more , Dolati S, Baziar N, Amirpour M, Zamanian G, Zamani O, Zavareh MAT, Akbari ME, Akbari A, Alamdari NM, Javid Z, Rahmani J, Ardehali SH, Shadnoush M
BMC Cancer · 2026 Jun · PMID 42316063 · Full text
BACKGROUND: Malnutrition is highly prevalent in cancer patients, leading to increased post-surgical complications. This umbrella review of meta-analyses aims to investigate the effect of immunonutrition on surgery outcom...
BACKGROUND: Malnutrition is highly prevalent in cancer patients, leading to increased post-surgical complications. This umbrella review of meta-analyses aims to investigate the effect of immunonutrition on surgery outcomes in Cancer patients. METHODS: MEDLINE/PubMed, SCOPUS, and WOS databases were investigated from their inception until Sep 2025. Meta-analysis investigating the impact of immunonutrition (or its components) on overall complications, infectious complications, non-infectious complications, mortality, surgical-site infections, anastomotic leak, and length of hospital stay in patients with cancer. Pooled effect sizes and CIs were calculated using a random-effects model. RESULTS: Fifty-four studies were included in the umbrella review. The pooled results showed RR = 0.79; 95%CI: 0.70-0.88; I2 = 39.5% for postoperative overall complications, RR = 0.61; 95%CI: 0.58-0.65; I2 = 47.3% for infectious complications, RR = 0.88; 95%CI: 0.82-0.94; I2 = 0% for non-infectious complications, HR = 0.86; 95%CI: 0.74-0.99; I2 = 0% for mortality, RR = 0.66; 95%CI: 0.59-0.74; I2 = 6.5% for surgical-site infection, RR = 0.69; 95%CI: 0.62-0.77; I2 = 0% for anastomotic leak, and WMD=-1.75 days; 95%CI: -2.09,-1.41; I2 = 90.3% for length of hospital stay in immunonutrition intervention compared to control groups. Subgroup analysis by time of intervention showed that postoperative intervention is more effective in reducing overall complications (RR = 0.69; 95%CI:0.54-0.89) and the length of hospital stay (2.26 days, P = 0.001) compared to preoperative or perioperative intervention. CONCLUSION: Cancer patients undergoing surgery may benefit from immunonutrition. Postoperative intervention is more effective than pre-or perioperative intervention.
Hepatorenal protective and antitumor effects of astaxanthin-loaded chitosan nanoparticles against ehrlich ascites carcinoma in mice through antioxidant, anti-inflammatory, and apoptotic pathway modulation.
Alfawaz MS, Elmorsy EM, Al Doghaither HA … +5 more , Al-Ghafari AB, Mansour AA, Alshammari AN, Fawzy MS, Elghareeb MM
BMC Cancer · 2026 Jun · PMID 42310631 · Full text
BACKGROUND: Ehrlich ascites carcinoma (EAC) is an aggressive experimental tumor model associated with severe oxidative stress, inflammation, and hepatorenal injury. Astaxanthin (ASX), a potent natural antioxidant caroten...
BACKGROUND: Ehrlich ascites carcinoma (EAC) is an aggressive experimental tumor model associated with severe oxidative stress, inflammation, and hepatorenal injury. Astaxanthin (ASX), a potent natural antioxidant carotenoid, has demonstrated anticancer and cytoprotective properties; however, its therapeutic application is limited by poor bioavailability and stability. Therefore, this study investigated the anticancer and hepatorenal protective effects of astaxanthin-loaded chitosan nanoparticles (ASX-CNPs) compared with free ASX in EAC-bearing mice. METHODS: Ninety female Swiss albino mice were randomly allocated into six groups: control, ASX, ASX-CNPs, EAC, EAC + ASX, and EAC + ASX-CNPs. Tumor progression, survival rate, oxidative stress biomarkers, inflammatory mediators, apoptotic markers, and histopathological alterations in hepatic and renal tissues were evaluated. Antioxidant parameters included SOD, CAT, GPx, GSH, TAC, and TBARS. Inflammatory and apoptotic signaling pathways were assessed through measurement of COX-2, TNF-α, IFN-γ, IL-1β, Bcl-2, Bax, and caspase-3 expression levels. RESULTS: ASX-CNPs markedly suppressed tumor progression and improved survival compared with free ASX. Treatment with ASX-CNPs significantly downregulated Bcl-2 expression while upregulating Bax and caspase-3, indicating enhanced apoptotic activity. Antioxidant defenses were significantly restored, as evidenced by increased SOD, CAT, GPx, GSH, and TAC levels, alongside reduced TBARS. Inflammatory responses were attenuated through decreased COX-2 activity and reduced TNF-α, IFN-γ, and IL-1β levels. Histopathological examination confirmed substantial protection against EAC-induced hepatic and renal damage. Overall, ASX-CNPs demonstrated greater therapeutic efficacy than free ASX across biochemical, molecular, and histopathological assessments. CONCLUSIONS: ASX-loaded chitosan nanoparticles exerted potent anticancer, antioxidant, anti-inflammatory, and hepatorenal protective effects in EAC-bearing mice. The enhanced efficacy of ASX-CNPs relative to free ASX is likely attributable to improved bioavailability and targeted modulation of oxidative stress, inflammatory, and apoptotic pathways, supporting their potential as a promising nanotherapeutic strategy for cancer-associated organ injury.
Cumulative incidence and prognostic factors for leukemic transformation in chronic myelomonocytic leukemia: a competing risk analysis.
Huang J, Zheng C, Liu Y … +2 more , Li C, Xin X
BMC Cancer · 2026 Jun · PMID 42310629 · Full text
BACKGROUND: Leukemic transformation represents a pivotal event in the natural history of chronic myelomonocytic leukemia (CMML), yet conventional survival analysis may yield biased estimates by treating non-transformatio...
BACKGROUND: Leukemic transformation represents a pivotal event in the natural history of chronic myelomonocytic leukemia (CMML), yet conventional survival analysis may yield biased estimates by treating non-transformation deaths as censored observations. We hypothesised that competing risk methodology would provide more accurate transformation estimates and could alter the interpretation of treatment-associated effects compared with traditional approaches. METHODS: We retrospectively analysed 102 patients with CMML diagnosed and treated at Ganzhou People's Hospital between January 2014 and November 2025. Cumulative incidence functions (CIF) were estimated using the Aalen-Johansen method with death without transformation as the competing event. Fine-Gray subdistribution hazard models identified independent predictors, with parallel Cox regression for methodological comparison. Treatments were classified by primary modality at baseline (HMA, chemotherapy, best supportive care (BSC), allo-HSCT) and entered as a stratification covariate rather than as a randomised exposure. RESULTS: During follow-up, 54 patients (52.9%) developed acute myeloid leukemia and 7 (6.9%) died without transformation. The 12-, 24-, and 36-month CIF were 46.9%, 63.4%, and 73.8%, respectively, whereas 1 - Kaplan-Meier estimates were 49.2%, 67.2%, and 78.4% (4.9-6.2% relative overestimation). Baseline treatment strategy was associated with transformation risk: compared with HMA, BSC showed a higher subdistribution hazard (SHR 4.77, 95% CI 1.86-12.22, P = 0.001) and chemotherapy SHR 2.16 (1.04-4.48, P = 0.039), with allo-HSCT not significantly associated (SHR 0.52, P = 0.261); these associations should be interpreted as exploratory given non-random allocation and small subgroup sizes (allo-HSCT n = 13, BSC n = 22). Intermediate and high-risk karyotypes independently predicted transformation (SHR 3.09 and 2.98, both P < 0.05). Within the NGS-tested subgroup, SETBP1 (SHR 3.09, P = 0.009) and TP53 (SHR 3.66, P = 0.009) mutations marked small subsets at very high transformation risk. For allo-HSCT, Cox regression yielded a significant protective effect (HR 0.31, P = 0.026) that became non-significant in the Fine-Gray model, illustrating how cause-specific analysis can overstate the isolated anti-transformation effect of a treatment that simultaneously reduces mortality. CONCLUSIONS: This study shows how competing-risk analysis complements standard Kaplan-Meier estimates of overall and progression-free survival when the cumulative incidence of a specific event, leukaemic transformation, is the quantity of interest. Although the modest, single-centre sample and non-randomised treatment allocation preclude definitive treatment recommendations, cytogenetic risk was the strongest disease-related prognostic factor, and molecular profiling provided additional risk discrimination within the NGS-tested subgroup. Cumulative incidence functions should therefore be reported routinely alongside Kaplan-Meier estimates in CMML and other myeloid neoplasms with non-negligible competing mortality.
Ablative ultra-hypofractionated radiotherapy with surgical GI exclusion as a "functional spacer" for pancreatic cancer: a phase I safety and feasibility study.
Di Y, Xia T, Wang Y … +1 more , Ren G
BMC Cancer · 2026 Jun · PMID 42310617 · Full text
OBJECTIVES: The therapeutic window for radiotherapy in locally advanced pancreatic cancer (LAPC) is severely constrained by the anatomical proximity of the duodenum. We hypothesized that radiation-induced gastrointestina...
OBJECTIVES: The therapeutic window for radiotherapy in locally advanced pancreatic cancer (LAPC) is severely constrained by the anatomical proximity of the duodenum. We hypothesized that radiation-induced gastrointestinal (GI) injury is exacerbated by physiological digestion, and that surgically bypassing the irradiated duodenum would provide a biological "functional spacer." We aimed to evaluate the safety and clinical feasibility of ablative ultra-hypofractionated radiotherapy (UHRT) followed directly by elective GI exclusion surgery. METHODS: In this prospective Phase I protocol, 10 patients with LAPC received ablative UHRT using Helical Tomotherapy at a prescribed dose of 40-60 Gy in 5 fractions. A prophylactic GI exclusion surgery (gastric truncation and GI bypass) was strictly scheduled within 7 days post-radiotherapy to place the high-dose irradiated duodenal segment into physiological quiescence. The primary endpoint was treatment safety assessed via CTCAE v4.02 and technical feasibility. RESULTS: All participants provided written informed consent and successfully completed the combined radiotherapeutic and surgical protocol. After a median follow-up of 12 months, no Grade 4-5 toxicities, bleeding, or gastrointestinal perforations were recorded. Only one patient (10%) experienced Grade 3 GI toxicity (abdominal pain). The Objective Response Rate (ORR) was 50%, with a 1-year overall survival rate of 60%. Furthermore, 70% of symptomatic patients achieved significant cancer-related pain relief. CONCLUSIONS: Preliminary results suggest that the integration of ablative UHRT with an immediate prophylactic surgical GI bypass is a feasible and safe protocol. This "functional spacer" concept potentially mitigates the duodenal dose-limiting bottleneck, allowing the practical delivery of biologically ablative radiation doses in LAPC without catastrophic GI consequences. However, larger multi-center trials are warranted for further validation. TRIAL REGISTRATION: Not prospectively registered. At the time of study initiation in 2015, this investigator-initiated, single-center exploratory Phase I safety and technical feasibility study was reviewed and approved by the Institutional Ethics Committee of Air Force Medical Center, PLA, and public trial registration was not requested by the committee. The study was not designed as a randomized comparative efficacy trial, but rather as a pilot evaluation of the safety and feasibility of an individualized combined radiotherapy-surgical strategy. The protocol was approved by the Institutional Ethics Committee of Air Force Medical Center, PLA (Approval No. 2015-118-S01) on 12 March 2015.
Self-perceived burden and quality of life in patients with radiation-induced brain injury after radiotherapy for nasopharyngeal carcinoma: a cross-sectional study on the mediating role of stigma and the moderating role of sleep quality.
Ye Y, Song R, Zhao F … +1 more , Chen L
BMC Cancer · 2026 Jun · PMID 42310606 · Full text
BACKGROUND: Although self-perceived burden (SPB), stigma and sleep quality are associated with quality of life (QoL) in patients with radiation-induced brain injury (RBI) after radiotherapy for nasopharyngeal carcinoma (...
BACKGROUND: Although self-perceived burden (SPB), stigma and sleep quality are associated with quality of life (QoL) in patients with radiation-induced brain injury (RBI) after radiotherapy for nasopharyngeal carcinoma (NPC), little is known about the mechanism underlying the relationship among these variables. The aim of this study was to examine the relationship among SPB, stigma, and QoL, and further explore how sleep quality may moderate the effect of stigma. METHODS: This cross-sectional study investigated 150 NPC patients with RBI who were recruited from an affiliated hospital of the university in Guangzhou, China. The participants completed several questionnaires, including a socio-demographic characteristics questionnaire, the Chinese version of the Self-Perceived Burden Scale (SPBS), the Social Impact Scale (SIS), the World Health Organization Quality of Life Instrument Short Form (WHOQOL-BREF), and the Pittsburgh Sleep Quality Index (PSQI). The mediation analysis and moderated mediation analysis were conducted using PROCESS macro Model 4 and Model 58 in SPSS 28, respectively. RESULTS: The results of mediation analysis showed that stigma had a significant indirect effect between self-perceived burden and quality of life (effect = -0.152, 95% CI = -0.223 to -0.032), and the direct effect of self-perceived burden on quality of life was not statistically significant (effect = -0.083, 95% CI = -0.300 to 0.134). In the moderated mediation analysis, the indirect effect of self-perceived burden on quality of life as mediated by stigma was apparent only among patients with poorer sleep quality (higher PSQI scores; effect = -0.115, 95% CI = -0.246 to -0.021). CONCLUSIONS: The findings suggest that stigma may function as a mechanism through which self-perceived burden is associated with quality of life in NPC patients with RBI, especially when patients suffer low sleep quality. Healthcare providers should pay attention to sleep quality and consider developing a supportive care intervention to improve patients' quality of life by incorporating effective strategies to reduce self-perceived burden and stigma for this population.
Molecular characteristics and clinicopathology of CTNNB1-mutated endometrial cancer: Implications for fertility-sparing management in young women.
Li WQ, Wu HX, Li HB … +3 more , Shuai GN, Zhang Q, Shen Y
BMC Cancer · 2026 Jun · PMID 42310566 · Full text
BACKGROUND: The incidence rate of endometrial cancer (EC) is increasing among young women who require fertility preservation. The identification of molecular biomarkers can improve clinical outcomes in these patients. Th...
BACKGROUND: The incidence rate of endometrial cancer (EC) is increasing among young women who require fertility preservation. The identification of molecular biomarkers can improve clinical outcomes in these patients. This study evaluated the role of CTNNB1 mutations in EC and whether the CTNNB1 gene can serve as a molecular marker in fertility-sparing management. METHODS: Retrospective cohorts of patients with pathologically confirmed EC were included in the study. The molecular landscape and TCGA-based molecular classification were analyzed through targeted next-generation sequencing and immunohistochemistry. The clinicopathological and molecular characteristics of CTNNB1-mutated and CTNNB1-wild-type patients were assessed. For young patient who received fertility-sparing treatment (FST), the responses to progestin treatment were evaluated. RESULTS: CTNNB1 mutations were significantly more common in the age group ≤ 40 years than in the age group > 40 years, indicating that CTNNB1 had a significant role in young patients with EC seeking fertility preservation. Most cases carrying CTNNB1 mutations were in the no specific molecular profile group. The most frequent CTNNB1 hotspot mutations were Ser37Phe on exon3 (16.13%). Moreover, CTNNB1 mutations were significantly associated with higher rates of endometrioid EC (p = 0.0001) and earlier stages (FIGO I or II) than the absence of mutations (p = 0.0457). Nonetheless, there were no significant differences in other pathological risk factors between the mutant and wild-type groups. The immunohistochemical expression of β-catenin can be used as a surrogate for CTNNB1 mutation status; nonetheless, specificity was associated with the frequency of CTNNB1 mutations. Patients with CTNNB1 mutations showed poor response to progestin treatment, possibly because of the reduced expression of progesterone receptors since the nuclear expression of β-catenin in the endometrium was negatively correlated with progesterone receptor expression. CONCLUSIONS: CTNNB1 status in EC can help predict the response to fertility-sparing treatment, allowing early stratification and risk assignment.
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