BMC Cancer[JOURNAL]
Sun
200 papers
Catastrophic health expenditure and its determinant factors among patients with cancer attending Wolaita Sodo University Comprehensive Specialized Hospital, South Ethiopia.
Tafese S, Balta B
BMC Cancer · 2026 Jul · PMID 42393580 · Full text
BACKGROUND: Cancer patients often face catastrophic health expenditures (CHE), leading to significant financial burdens for households. When cancer treatment depends mainly on out-of-pocket payments, the risk of incurrin...
BACKGROUND: Cancer patients often face catastrophic health expenditures (CHE), leading to significant financial burdens for households. When cancer treatment depends mainly on out-of-pocket payments, the risk of incurring CHE increases; thus, this study assessed the incidence and key factors contributing to CHE among cancer patients. METHODS: A cross-sectional study was conducted at Wolaita Sodo University Comprehensive Specialized Hospital, including 294 cancer patients selected systematically. Data were analyzed using SPSS version 27, with bivariable and multivariable logistic regression models used to assess associations between CHE and independent variables. RESULTS: Among cancer patients, the incidence of catastrophic health expenditure (CHE) at a 40% threshold was 83.7% (95% CI: 78.9-87.4). Medication cost constituted the largest treatment expense, accounting for 66.7% of total costs. Multivariable analysis identified three independent factors significantly associated with CHE: lack of formal education (AOR = 3.6; 95% CI: 1.1-12.0), absence of health insurance (AOR = 3.2; 95% CI: 1.5-7.0), and cancer diagnosis in private facilities (AOR = 4.2; 95% CI: 3.5-13.7). CONCLUSION: The incidence of catastrophic health expenditure (CHE) was higher than reported in published studies. Key contributing factors included lack of insurance, educational status, and diagnosis at private healthcare facilities, all of which exacerbated financial hardship. Expanding community-based health insurance (CBHI) is essential, especially for low-income households. Furthermore, hospitals should enhance access to cancer diagnostic services to help alleviate the financial burden of diagnosis.
Single-session agreement of ChatGPT and Gemini treatment recommendations with multidisciplinary tumor board decisions in thoracic oncology.
Hasimoglu Gurun K, Cikladilmez F, Demirag G … +1 more , Yilmaz B
BMC Cancer · 2026 Jul · PMID 42393575 · Full text
BACKGROUND: To evaluate the single-session agreement between treatment recommendations generated by ChatGPT and Gemini and real-world decisions made by a thoracic oncology multidisciplinary tumor board (MDTB). METHODS: T...
BACKGROUND: To evaluate the single-session agreement between treatment recommendations generated by ChatGPT and Gemini and real-world decisions made by a thoracic oncology multidisciplinary tumor board (MDTB). METHODS: This retrospective observational study included 102 thoracic oncology cases discussed at a university hospital MDTB between June and December 2025. Cases were categorized as primary lung cancer, pulmonary mass without pathological diagnosis, esophageal cancer, or pulmonary metastasis. Standardized anonymized case summaries, including clinical, radiological, pathological, and laboratory data, were presented to ChatGPT and Gemini. Each model was asked to provide a single tumor board-like management recommendation. Each case was submitted once to each model in a separate new chat session, and the initial output was used for analysis. Recommendations were classified into predefined categories and compared with final MDTB decisions. Agreement was assessed using percentage agreement and Cohen's kappa coefficient. RESULTS: In this single-session evaluation, overall agreement with MDTB decisions was 52.0% for ChatGPT and 56.9% for Gemini. Both models showed moderate agreement, with slightly higher agreement for Gemini than ChatGPT (κ = 0.487 vs. κ = 0.432; p < 0.001). Agreement was higher in standardized scenarios, such as primary lung cancer and esophageal cancer, but lower in pulmonary masses without pathological diagnosis and pulmonary metastases. No significant difference was found between the models in overall concordance with MDTB decisions (p = 0.359). CONCLUSION: The initial outputs of ChatGPT and Gemini showed moderate agreement with MDTB decisions in this single-session evaluation. LLMs may support guideline-based thoracic oncology decision-making but remain limited in complex, patient-specific scenarios and should not replace multidisciplinary clinical judgment. These findings should be interpreted as concordance with real-world MDTB decisions rather than evidence of stable model-level performance or clinical accuracy.
Pleomorphic adenoma: does the immunohistochemical profile direct the clinical profile: retrospective study and review of literature.
Alnour A
BMC Cancer · 2026 Jul · PMID 42393573 · Full text
BACKGROUND: Pleomorphic adenoma is a benign salivary gland tumor that has a potentiality to recurrence and malignant transformation as well. The genetic alteration of this tumor is not completely studied yet. Investigati...
BACKGROUND: Pleomorphic adenoma is a benign salivary gland tumor that has a potentiality to recurrence and malignant transformation as well. The genetic alteration of this tumor is not completely studied yet. Investigating the growth factor receptors and tumor microenvironment may yield answers to the nature of this tumor. METHODS: Thirty-six formalin-fixed, paraffin-embedded pleomorphic adenoma specimens were collected from Al-Mouassat University Hospital. EGFR, HER-2 and BCL-2 antibodies have been used in immunohistochemistry stains to investigate the most probable affected pathway in this progress of this tumor. RESULTS: Immunohistochemical analysis revealed total negativity for HER2 expression. While, EGFR and BCL-2 expression was positive in diffuse patchy pattern. The positivity was membranous and/or cytoplasmic predominantly within the tumor cell population. Statistical analysis revealed no significant association between EGFR/BCL-2 expression and patient gender (p = 0.848) or tumor site (p = 1.000). The absence of HER2 expression was consistent across all cases, regardless of clinicopathological parameters. The expression of EGFR and BCL2 did not show a statistically significant correlation with demographic variables, suggesting a tumor-intrinsic expression pattern rather than dependence on clinical factors. CONCLUSION: On this study, pleomorphic adenoma demonstrated a distinct immune-profile with positivity of EGFR and BCL-2 and negative expression of HER-2. These findings suggest HER-2 unlikely contribute to tumor behavior, meanwhile the positivity of EGFR and BCL-2 may be related to the tumor survival rather than malignant transformation. Moreover, these markers do not same to consider as reliable predictors of malignant transformation in pleomorphic adenoma.
Integrated bioinformatic multi-omics analysis and experimental verification reveal the oncogenic role of WDHD1 and its underlying mechanism in gastric cancer progression.
Wang X, Yu J, Sun Z … +7 more , Sun Y, Li K, Meng K, Kong J, Li G, Duan P, Yue X
BMC Cancer · 2026 Jul · PMID 42393565 · Full text
BACKGROUND: Gastric cancer (GC) is one of the most common malignancies worldwide. WD repeat and HMG-box DNA-binding protein 1 (WDHD1) has been identified as an oncogenic factor involved in the progression of hepatocellul...
BACKGROUND: Gastric cancer (GC) is one of the most common malignancies worldwide. WD repeat and HMG-box DNA-binding protein 1 (WDHD1) has been identified as an oncogenic factor involved in the progression of hepatocellular carcinoma, lung adenocarcinoma, nasopharyngeal carcinoma, and several other cancers. However, its role in GC remains insufficiently explored in the existing literature. METHODS: In this study, TCGA, GTEx, and GEO datasets were used to evaluate differences in WDHD1 expression between GC tissues and normal gastric tissues, and to analyze its associations with patient prognosis and clinicopathological characteristics. The CCLE database was used to assess WDHD1 expression levels in GC cell lines. The GDSC and CTRP pharmacogenomic databases were used to investigate the potential relationship between WDHD1 expression and sensitivity to antitumor agents. In addition, the TISCH2 single-cell database was used to analyze the distribution of WDHD1 expression across different cell populations in the GC tumor microenvironment and to preliminarily explore its association with the immune microenvironment. Subsequently, EdU, CCK-8, and colony formation assays were performed to evaluate the effect of WDHD1 on the proliferative capacity of GC cells, and a nude mouse xenograft tumor model was used to validate the regulatory role of WDHD1 in tumor growth in vivo. To further explore the potential underlying mechanisms, comparative proteomic analysis and cell-cycle flow cytometry were performed in WDHD1 knockdown cells and control cells, thereby preliminarily revealing the possible molecular mechanisms by which WDHD1 contributes to GC progression. RESULTS: WDHD1 was significantly overexpressed in GC, and its high expression was associated with poor prognosis and showed favorable diagnostic value. Functional enrichment analysis indicated that high WDHD1 expression was mainly associated with enrichment of pathways related to the cell cycle, DNA replication, and cell proliferation. In GC, WDHD1 downregulation exerted tumor-suppressive effects, inhibited DNA synthesis, and induced cell-cycle redistribution. CONCLUSION: WDHD1, as a key factor regulating DNA replication and cell cycle progression during GC progression, may serve as a potential molecular target for diagnosis, prognostic assessment, and therapeutic intervention in GC.
Correction: Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells.
de Castro E Gloria H, Nogueira LJ, Grudzinski PB … +4 more , da Costa Ghignatti PV, Guecheva TN, Leguisamo NM, Saffi J
BMC Cancer · 2026 Jul · PMID 42387504 · Full text
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PDCD1 gene polymorphisms linked with altered risk of female-specific hormone-dependent cancers: a systematic review and meta-analysis.
Zidi S, BenAbdelmoumenMardassi B, Sahraoui G … +1 more , Almawi WY
BMC Cancer · 2026 Jul · PMID 42387483 · Full text
BACKGROUND: The programmed cell death-1 (PDCD1) gene plays a critical role in immune regulation and tumor immune evasion, making it a key target in cancer immunotherapy. Genetic variants in PDCD1, including rs2227981, rs...
BACKGROUND: The programmed cell death-1 (PDCD1) gene plays a critical role in immune regulation and tumor immune evasion, making it a key target in cancer immunotherapy. Genetic variants in PDCD1, including rs2227981, rs2227982, rs7421861, and rs11568821, may influence susceptibility to female-specific cancers. This systematic review and meta-analysis aimed to evaluate the association of these variants with the risk of breast, cervical, ovarian, and endometrial cancers across ethnic populations. METHODS: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for studies published up to January 2025. Eligible studies were case-control in design and reported genotypic or allelic frequencies. Risk of bias was assessed using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under dominant, recessive, and allelic genetic models. Heterogeneity was evaluated using the I² statistic. Publication bias was assessed using funnel plots, Egger's test, and Begg's test. Sensitivity analyses were performed to evaluate the robustness of the results. RESULTS: Eleven case-control studies were included, comprising 3534 breast cancer, 1468 cervical cancer, 1160 ovarian cancer, and 873 endometrial cancer cases, each with corresponding controls. The rs2227981 C allele and rs2227982 T allele were significantly associated with increased risk of female-specific cancers (p < 0.0001). Similarly, rs7421861 and rs11568821 showed significant associations across multiple genetic models. Heterogeneity ranged from low to high (I² = 19.5%-84%). No significant publication bias was detected (Egger's test p = 0.586; Begg's test p = 0.548). However, variability between studies and limited sample sizes should be considered when interpreting the findings. CONCLUSIONS: PDCD1 gene polymorphisms are associated with susceptibility to female-specific cancers, underscoring the importance of genetic variability in immune regulation and oncogenesis. Further large-scale and functional studies are needed to validate these findings and to explore gene-environment interactions.
Comparative effectiveness of radical surgery versus concurrent chemoradiotherapy in stages IB3, IIA2, or locally resectable IIICr cervical cancer: a prospective, multicenter, propensity score-matched cohort study.
Liu Q, Liu W, Huang Y … +9 more , Li Y, Jiang L, Sun S, Qu X, Lv B, Fu J, Yao Y, Qiu J, Hua K
BMC Cancer · 2026 Jul · PMID 42387473 · Full text
BACKGROUND: While concurrent chemoradiotherapy (CCRT) is the standard first-line treatment, radical surgery (RS) is frequently preferred in China, despite unclear comparative efficacy. The role of minimally invasive surg...
BACKGROUND: While concurrent chemoradiotherapy (CCRT) is the standard first-line treatment, radical surgery (RS) is frequently preferred in China, despite unclear comparative efficacy. The role of minimally invasive surgery also remains controversial and requires further validation. These persistent uncertainties underscore the need to advance research into LACC treatment strategies. METHODS: We conducted a multicenter prospective cohort study at three tertiary teaching hospitals in Shanghai, including 246 patients with specific locally advanced cervical cancer (LACC; FIGO 2018 stages IB3, IIA2, or locally resectable IIICr). We compared overall survival (OS), progression-free survival (PFS), adverse events (AEs), two-year quality-adjusted life years (QALYs), and treatment costs between RS (n = 198) and definitive CCRT (n = 48). We also compared tumor-free laparoscopic RS (n = 119) with open RS (n = 79) within the RS cohort. Propensity score matching (PSM) was applied to reduce potential confounding. Subgroup and sensitivity analyses were performed to assess the robustness of the results. RESULTS: After PSM, there were no significant differences in OS or PFS between the RS and definitive CCRT groups (two-year OS: 92% [86-97%] vs. 91% [82-100%]; two-year PFS: 79% [72-87%] vs. 78% [66-91%]), nor between the tumor-free laparoscopic and open RS groups (two-year OS: 97% [93-100%] vs. 91% [84-98%]; two-year PFS: 82% [74-92%] vs. 78% [69-89%]). Subgroup and sensitivity analyses yielded consistent findings. Two-year QALYs were comparable between the RS and definitive CCRT groups (23.55 [22.54, 24.00] vs. 23.53 [22.60, 23.80] months; W = 3148, p = 0.074), but significantly higher in the tumor-free laparoscopic RS group than in the open RS group (24.00 [23.52, 24.00] vs. 23.52 [21.77, 24.00] months; W = 3060, p = 0.003). The median total treatment cost was significantly higher in the RS group than in the definitive CCRT group (96,879 [91,400-104,815] CNY vs. 83,555 [73,790-95,554] CNY; W = 347.000, p = 0.018). CONCLUSIONS: RS and definitive CCRT provided comparable short-term survival outcomes and two-year QALYs in specific LACC patients, although the RS group tended to be associated with higher treatment costs. Within the surgical cohort, tumor-free laparoscopic RS achieved similar survival outcomes to open RS but offered better two-year QoL benefits, supporting its role as a potential surgical option under strict oncologic principles.
Analysis of factors influencing SARS-CoV-2 infection and outcomes in patients with chronic lymphocytic leukemia during the burst of COVID-19 epidemic.
Wang J, Wang S, Xu F … +5 more , Hu H, Liu YP, Liang XG, Feng GP, Chen B
BMC Cancer · 2026 Jul · PMID 42387447 · Full text
BACKGROUND: CLL patients have immune deficiencies and are at high risk of SARS-CoV-2 infection. Limited research exists on risk factors and survival outcomes of SARS-CoV-2 infection in Asian CLL patients during the COVID...
BACKGROUND: CLL patients have immune deficiencies and are at high risk of SARS-CoV-2 infection. Limited research exists on risk factors and survival outcomes of SARS-CoV-2 infection in Asian CLL patients during the COVID-19 pandemic. Therefore, this study aims to explore the relationship between SARS-CoV-2 infection and survival in this population. METHODS: A retrospective analysis was conducted on 119 CLL patients treated at a large tertiary comprehensive hospital in western China from January 2020 to May 2023, coinciding with a surge in the epidemic in the city. RESULTS: (1) During the epidemic, the treatment group had a higher proportion of males, second-line and initial treatment, 11q- chromosome, LDH level, and lower erythrocyte count (P < 0.05). Patients in this group had longer median duration of malaise, more headaches and coughs, longer cough and sputum duration, higher rates of hyposmia, and more patients received antiviral treatment for COVID-19 and suffered weight loss. The treatment group had more CLL patients affected by SARS-CoV-2, and more patients developed secondary COVID-19 infection, and had lower RBC count and hemoglobin levels (P < 0.05). (2) Compared to the non-BTKi treatment group, more patients in BTKi treatment received treatment lasting ≥ 1 month, more had abnormal karyotyping, high-risk cytogenetics, less recent cytotoxic drug and rituximab exposure, lower lymphocyte count, elevated creatinine level, and lower glomerular filtration rate (P < 0.05). (3) Firth's penalised-likelihood logistic regression revealed that male sex increased hospitalization risk, while normal karyotyping decreased this risk. Male sex and recent rituximab exposure (within 6 months) were SARS-CoV-2 infection risk factors. Both frontline and second-or-more line therapies were associated with higher SARS-CoV-2 mortality risk compared to untreated patients (all P < 0.05). CONCLUSION: Male sex and recent exposure to rituximab within the past six months are risk factors for SARS-CoV-2 infection in CLL patients. Both frontline and second-or-more line therapies are risk factors for mortality (compared to untreated patients). Treatment with BTK inhibitors does not increase the risk of SARS-CoV-2 infection or mortality.
Human single domain antibody-based CAR-T cells targeting BAFF-R demonstrate promising preclinical activity in B-cell malignancies.
Zhang C, Luo Q, Wu S … +8 more , Xu L, Wei Q, Zhang Y, Guan C, Dong X, Hong Y, Tan T, Chen B
BMC Cancer · 2026 Jul · PMID 42387444 · Full text
BACKGROUND: Single-chain antibody-based CAR-T cells targeting BAFF-R have demonstrated antitumor effects against human B-cell malignancies and can overcome CD19 antigen loss. However, CARs built on antigen-specific singl...
BACKGROUND: Single-chain antibody-based CAR-T cells targeting BAFF-R have demonstrated antitumor effects against human B-cell malignancies and can overcome CD19 antigen loss. However, CARs built on antigen-specific single-chain antibody variable fragments may have limitations, e.g., large CAR binding domain size. To improve the function of BAFF-R CAR-T cells, we designed CARs with only a fully human heavy-chain variable domain. METHODS: A fully human antibody phage display library was used to select anti- BAFF- R clones using protein/cell alternate panning. The screened clones were grafted into a second-generation CAR to generate CAR-T cells. CD107a degranulation, luciferase-based cytolysis, repeat antigen stimulation, activation markers, and exhaustion markers were used to detect the function of CAR-T cells in vitro. Xenografts were established in NPG mice following intravenous injection of Jeko-1 cells. Tumor burden and survival of mice were recorded weekly. RESULTS: Three single-domain heavy chain antibodies, namely Clone #5, Clone #77, and Clone #80, were selected for further evaluation. CAR-T cells constructed with these three candidate clones demonstrated specific target cell activation and effective cytotoxicity in vitro. Clone #5 and Clone #77 CAR-T cells exhibited superior cytotoxic capacity and expansion ability. No significant difference was observed in the expression levels of exhaustion markers on the surface of the three CAR-T cell types. In vivo studies revealed that Clone #5 CAR-T cells displayed enhanced antitumor efficacy compared to other groups, resulting in prolonged survival. CONCLUSION: We developed a novel BAFF-R CAR-T cell product structured on a fully human single-domain antibody. This product demonstrated promising preclinical activity and may provide a potential alternative treatment for patients with B-cell malignancies.
Network-based integrative transcriptomic analysis reveals immune-regulatory and oncogenic signatures of EOMES and SPRYD3 in head and neck squamous cell carcinoma.
He L, Zeng Y, Gao Y … +2 more , Xie X, Liu Y
BMC Cancer · 2026 Jul · PMID 42387439 · Full text
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) exhibits marked heterogeneity driven by both tumor-intrinsic programs and immune context. However, the relationship between epithelial proliferation and immune ac...
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) exhibits marked heterogeneity driven by both tumor-intrinsic programs and immune context. However, the relationship between epithelial proliferation and immune activity remains incompletely defined. METHODS: We combined bulk transcriptomic analyses of HNSCC cohorts (GSE83519 and TCGA-HNSC) with single-cell RNA sequencing data derived from OSCC (GSE172577) to identify gene programs associated with tumor progression. Co-expression network analysis was used to identify tumor-related modules, and candidate genes were evaluated by survival analysis and experimental validation. Single-cell analysis of an OSCC cohort and CopyKAT-based epithelial cell identification were performed to define cell-type-specific expression patterns. RESULTS: EOMES and SPRYD3 were identified as candidate prognostic markers associated with distinct biological programs. Single-cell analysis showed that SPRYD3 expression was enriched in aneuploid epithelial cells, whereas EOMES expression was restricted to cytotoxic lymphocyte populations. Tumor epithelial cells with high SPRYD3 expression exhibited activation of cell cycle and DNA replication pathways, while immune-related signaling was reduced. In contrast, EOMES expression was associated with interferon response and T-cell effector programs. Experimental validation supported increased SPRYD3 expression, whereas EOMES exhibited a tendency toward lower expression in OSCC tissues. CONCLUSIONS: SPRYD3 and EOMES represent distinct transcriptional programs associated with epithelial proliferation and immune activity in HNSCC. These findings provide a framework for understanding tumor-immune interactions and highlight the potential prognostic and biological relevance of EOMES and SPRYD3 in HNSCC.
Complications and survival after Ivor Lewis esophagectomy.
Abu Hejleh A, Lemties J, Kreutzer I … +10 more , Wirsik NM, Krauss DT, Torabi S, Jung JO, Schröder W, Schlößer HA, Schmidt T, Fuchs HF, Bruns CJ, Schiffmann LM
BMC Cancer · 2026 Jul · PMID 42387428 · Full text
BACKGROUND: Esophagectomy (OE) remains a complex procedure with a considerable risk of severe postoperative complications. There is conflicting evidence if major postoperative complications impair long-term oncological s...
BACKGROUND: Esophagectomy (OE) remains a complex procedure with a considerable risk of severe postoperative complications. There is conflicting evidence if major postoperative complications impair long-term oncological survival. This retrospective study was designed to retest the hypothesis that complications after OE impact on long-term survival in a large and highly standardized cohort of esophageal cancer patients. MATERIALS AND METHODS: 733 patients who underwent Ivor Lewis esophagectomy (IL-OE) for cancer from 2016 to 2021 at our tertiary center were analysed from a prospectively maintained database. Postoperative complications were correlated to overall survival. RESULTS: Neither occurrence of major complications ≥ Clavien-Dindo (CD) IIIB (Median OS not reached in both groups, p = 0.45, HR 1.12) nor AL (Median OS not reached for no AL vs. 50 months for AL, p = 0.49, HR 0.96) nor pulmonary complications (Median OS not reached in both groups, p = 0.61, HR 0.76) had an impact on overall survival. However, the necessity for postoperative readmission to ICU (reaICU) had a significant impact on overall survival (Median OS not reached for no reaICU vs. 40 months for reaICU, p = 0.037, HR 1.54). Mean follow up was 27 months. CONCLUSION: Among all variables, only ICU readmission significantly affected overall survival. Postoperative complications and in particular anastomotic leakage after IL-OE, per se, may have a less significant impact on overall survival than previously anticipated. This might be due to a highly sufficient management of complications that progressively avoids requirement of severe septic complications and intensive care treatment.
ITGAX is associated with poor prognosis and an immune-inflammatory microenvironment in clear cell renal cell carcinoma.
Chen X, Lin Z, Zhang R … +4 more , Xie H, Kong W, Fu Z, Pei X
BMC Cancer · 2026 Jul · PMID 42387425 · Full text
BACKGROUND: Integrin alpha X (ITGAX, CD11c) functions as a leukocyte adhesion molecule vital for immune cell activation, antigen presentation, and inflammatory responses. However, the expression profile, clinical relevan...
BACKGROUND: Integrin alpha X (ITGAX, CD11c) functions as a leukocyte adhesion molecule vital for immune cell activation, antigen presentation, and inflammatory responses. However, the expression profile, clinical relevance, immunoregulatory functions, and underlying mechanisms of ITGAX in clear cell renal cell carcinoma (ccRCC) remain incompletely elucidated. METHODS: ITGAX expression and its association with clinicopathological characteristics were examined using The Cancer Genome Atlas (TCGA)-kidney renal clear cell carcinoma (KIRC) dataset. Survival outcomes were analyzed using Kaplan-Meier and Cox regression methodologies. However, diagnostic efficacy was assessed via receiver operating characteristic (ROC) curve analysis. Immune cell infiltration, tumor purity, and immune checkpoint gene expression were evaluated using various computational algorithms. To elucidate the molecular features associated with ITGAX, functional enrichment and protein-protein interaction analyses were conducted. A KIRC single-cell RNA sequencing dataset was used to ascertain the cellular localization of ITGAX within the tumor microenvironment. In vitro validation involved the use of the ccRCC cell lines 786-O and Caki-1, alongside the normal renal epithelial cell line HK-2. ITGAX knockdown, functional assays, Western blotting, and AKT reactivation with SC79 were used to study cell phenotypes and the AKT/mTOR signaling pathway. RESULTS: ITGAX expression was markedly upregulated in TCGA-KIRC tissues and positively correlated with adverse clinicopathological characteristics, poorer overall survival, and favorable diagnostic efficacy, as evidenced by ROC curve analysis. Various computational algorithms indicated a strong association between ITGAX expression and immune cell infiltration, reduced tumor purity, elevated immune scores, and increased immune checkpoint gene expression. Functional enrichment analysis revealed that genes associated with ITGAX were predominantly involved in immune-related and microenvironment-associated pathways. Single-cell analysis demonstrated that ITGAX was predominantly enriched in myeloid cell populations, particularly monocytes/macrophages and dendritic cells, within the KIRC tumor microenvironment. In vitro experiments confirmed the relative elevation of ITGAX in ccRCC cell lines compared to HK-2 cells and revealed that ITGAX knockdown led to reduced cell proliferation, migration, invasion, and clonogenicity. ITGAX silencing was also associated with decreased AKT/mTOR phosphorylation, whereas AKT reactivation partially mitigated these phenotypic changes. CONCLUSIONS: This study suggests that ITGAX is associated with unfavorable clinical characteristics, a myeloid-enriched immune contexture, and AKT/mTOR-associated malignant phenotypes in ccRCC. These results suggest that ITGAX is a potential immune-related biomarker of ccRCC; however, additional clinical, spatial, and in vivo validation is necessary.
The impact of abiraterone and enzalutamide on hypokalemia incidence in patients with prostate cancer: a systematic review and meta-analysis.
Lou Y, Fan D, Chen T … +1 more , Xiong K
BMC Cancer · 2026 Jul · PMID 42387420 · Full text
OBJECTIVE: To systematically evaluate the incidence of hypokalemia associated with novel androgen receptor axis-targeted therapies (ARATs)-specifically abiraterone, enzalutamide, and their combination-in patients with ad...
OBJECTIVE: To systematically evaluate the incidence of hypokalemia associated with novel androgen receptor axis-targeted therapies (ARATs)-specifically abiraterone, enzalutamide, and their combination-in patients with advanced prostate cancer. METHODS: A comprehensive search of PubMed, Embase, and the Cochrane Library was conducted to identify published randomized controlled trials (RCTs). Risk of bias was assessed using the Cochrane Risk of Bias tool. A random-effects model was employed to pool risk ratios (RRs) and 95% confidence intervals (CIs). Heterogeneity was quantified using the I statistic, and subgroup analyses were stratified by the specific ARAT regimen. Publication bias was evaluated utilizing funnel plots. RESULTS: Eight unique RCTs (comprising 9 published reports) involving 9,298 patients were included. The overall pooled analysis demonstrated a significantly increased risk of all-grade hypokalemia in patients receiving ARATs compared to controls (RR = 3.11, 95% CI: 1.88-5.15, P < 0.001; I = 91.9%). Subgroup analyses revealed that this risk was significantly elevated with abiraterone (RR = 3.25, 95% CI: 1.75-6.02, I = 88.3%) and the combination of abiraterone plus enzalutamide (RR = 4.62, 95% CI: 2.65-8.03, I = 48.6%), but not with enzalutamide (RR = 1.16, 95% CI: 0.96-1.39). Similarly, the risk of severe (grade ≥ 3) hypokalemia was significantly higher with ARAT treatment (RR = 4.54, 95% CI: 2.42-8.51, I = 48.4%); the risk signal was strongest in combination regimens (RR = 9.34, 95% CI: 1.71-50.90), although this estimate was based on limited data. CONCLUSION: Based on our preliminary findings, ARAT therapies, particularly abiraterone and combination regimens, are significantly related to the increased risk of hypokalemia in patients with advanced prostate cancer. Vigilant monitoring and the proactive management of serum potassium levels are strongly warranted in clinical practice.
Delaying surgery beyond six weeks after systemic therapy reduces postoperative morbidity without evidence of impaired oncologic outcomes in colorectal liver metastases.
Giehl-Brown E, Nikbakhsh R, Mansourkiaei A … +8 more , Jötten L, Köhler BC, Longerich T, Kong B, Mehrabi A, Büchler MW, Al-Saeedi M, Kahlert C
BMC Cancer · 2026 Jun · PMID 42380904 · Full text
BACKGROUND: The optimal timing of resection for colorectal liver metastases (CRLM) after systemic therapy remains unclear. This study evaluated the impact of time-to-surgery (TTS) on postoperative morbidity and oncologic...
BACKGROUND: The optimal timing of resection for colorectal liver metastases (CRLM) after systemic therapy remains unclear. This study evaluated the impact of time-to-surgery (TTS) on postoperative morbidity and oncologic outcomes. METHODS: In this retrospective cohort (2018-2022) from a German high-volume hepatobiliary center, 159 patients underwent hepatic resection for CRLM following systemic therapy. Patients were stratified by TTS ≤ 41 versus ≥ 42 days. The primary endpoint was clinically meaningful postoperative morbidity (Comprehensive Complication Index ≥ 30). Secondary endpoints included liver-specific recurrence-free survival (RFS) and overall survival (OS). Multivariable regression, Cox proportional-hazards models, and prespecified subgroup analyses were performed. RESULTS: CCI ≥ 30 occurred in 48.7% of patients with shorter TTS versus 31.3% with longer TTS (P = 0.023). After multivariable adjustment, TTS ≥ 42 days was independently associated with lower odds of postoperative morbidity (OR 0.355; 95% CI 0.127-0.992; P = 0.048). In the subgroup of major hepatectomies, TTS ≥ 42 days demonstrated an even more pronounced protective effect (OR 0.069; 95% CI 0.006-0.778; P = 0.031). However, TTS ≥ 42 days was not independently associated with liver-specific RFS or OS. CONCLUSION: Delaying surgery to ≥ 6 weeks after neoadjuvant systemic therapy was associated with significantly reduced postoperative morbidity without evidence of impaired early oncologic outcomes among patients who ultimately underwent resection. These findings support consideration of a prolonged interval before complex hepatectomy while highlighting the need for prospective validation.
Perioperative NLR/PLR dynamic phenotypes and prediction of postoperative recurrence in locally advanced gastric cancer: a retrospective cohort study.
Wu Y, Zhou J, Li S … +2 more , Xuan Y, Cai D
BMC Cancer · 2026 Jun · PMID 42380878 · Full text
BACKGROUND: Systemic inflammation plays a critical role in tumor progression and postoperative recurrence in gastric cancer. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are readily acc...
BACKGROUND: Systemic inflammation plays a critical role in tumor progression and postoperative recurrence in gastric cancer. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are readily accessible biomarkers of systemic inflammatory and immune responses, but their dynamic changes around surgery remain underexplored. This study aimed to assess the prognostic value of principal component-derived phenotypes based on perioperative NLR and PLR-specifically, principal component 1 (PC1; preoperative inflammatory burden) and principal component 2 (PC2; postoperative inflammatory recovery dynamics)-for predicting disease-free survival (DFS) in patients with locally advanced gastric cancer (LAGC). METHODS: We retrospectively analyzed data from 375 patients with LAGC who underwent radical gastrectomy at the Affiliated Hospital of Jiangnan University between January 2018 and December 2022, with follow-up through March 2025. NLR and PLR were measured one week before and one month after surgery. Principal component analysis (PCA) was applied to derive two independent inflammatory phenotypes (PC1 and PC2). These components, together with T stage, N stage, and preoperative carcinoembryonic antigen (CEA), were incorporated into a Cox proportional hazards regression model, and internal validation was performed using bootstrap resampling (1000 times). Model performance was evaluated using Kaplan-Meier survival analysis, log-rank testing, and time-dependent receiver operating characteristic (ROC) curve analysis. RESULTS: PCA identified two independent components: PC1 (preoperative inflammatory burden; variance explained 40.24%) and PC2 (postoperative inflammatory recovery; variance explained 36.16%). Multivariate Cox regression revealed that N stage, T stage, preoperative carcinoembryonic antigen (CEA), PC1, and PC2 were independent predictors of DFS (all p < 0.05). Stratified analysis demonstrated that patients with the "Dual-High" phenotype (high PC1 and high PC2) had a markedly shorter median DFS (13.1 months) compared with those with the "Dual-Low" phenotype (74.6 months; p < 0.001). Internal validation showed good discriminative ability of the model (bias-corrected concordance index [C-index] = 0.762), and time-dependent ROC curves indicated stable predictive performance at 12, 36, and 60 months postoperatively. CONCLUSIONS: PCA-derived perioperative inflammatory phenotypes effectively stratify recurrence risk in LAGC. The "Dual-High" phenotype indicates poor prognosis, and combining these phenotypes with T stage, N stage, and preoperative CEA enhances individualized postoperative surveillance and adjuvant therapy decision-making.
NT5E promotes colorectal cancer progression and correlates with PD-L1 expression: evidence from multi-omics analysis, clinical samples, and cellular functional assays.
Wu W, Cheng C, Yang T … +2 more , Meng W, Wang Y
BMC Cancer · 2026 Jun · PMID 42380875 · Full text
BACKGROUND: Extracellular 5'-nucleotidase (NT5E/CD73) plays a pivotal role in the tumor immune microenvironment by catalysing the production of adenosine. This study aims to evaluate the expression and function of NT5E i...
BACKGROUND: Extracellular 5'-nucleotidase (NT5E/CD73) plays a pivotal role in the tumor immune microenvironment by catalysing the production of adenosine. This study aims to evaluate the expression and function of NT5E in colorectal cancer progression, and to explore its potential as a novel biomarker and for associated immunotherapy. METHODS: Genomic alterations, prognostic significance, and immune landscape of NT5E were analyzed using cBioPortal, Kaplan‑Meier Plotter, the cancer genome atlas(TCGA)and the Human Protein Atlas. Following siRNA‑mediated knockdown in HCT116 cells, proliferation, migration, and invasion were assessed. NT5E and PD‑L1 expression were examined in 40 paired colorectal cancer specimens by qRT‑PCR. The regulatory relationship between PD‑L1 and NT5E was further validated in vitro. RESULTS: NT5E alterations were identified in 5.17% of CRC patients, primarily manifested as high mRNA expression and amplification. Elevated NT5E expression was significantly correlated with poorer overall survival and relapse‑free survival, particularly in patients with advanced stage, CMS1 (Consensus Molecular Subtypes 1), CMS4, and high microsatellite instability (MSI-H) subtypes. Gene set enrichment analysis revealed enrichment of purine metabolism, sphingolipid signaling, focal adhesion, and T cell receptor signaling pathways in NT5E‑high tumors. NT5E expression was positively correlated with helper T cells, macrophages, and mast cells, while negatively correlated with NK CD56dim cells. A significant positive correlation was observed between NT5E and PD‑L1, HAVCR2, and TIGIT. In clinical specimens, NT5E was upregulated in 65% of colorectal cancer tissues and positively associated with lymph node metastasis and PD‑L1 expression. In vitro experiments demonstrated that NT5E knockdown suppressed the proliferation, migration, and invasion of colorectal cancer cells, and confirmed that PD‑L1 regulates NT5E expression in colon cancer cells. CONCLUSION: NT5E accelerates disease progression by promoting malignant biological behaviors in colorectal cancer and synergistically shaping an immunosuppressive microenvironment with PD-L1. Its overexpression constitutes an independent adverse prognostic factor. This discovery offers novel insights for anti-PD-1/PD-L1 combination immunotherapy.
Optimized chemotherapy sequence for metastatic pancreatic ductal adenocarcinoma patients: FOLFIRINOX followed by Gemcitabine plus nab-paclitaxel.
Del Campo-Pedrosa R, Martín-Carnicero A, González-Marcos A … +1 more , Martínez A
BMC Cancer · 2026 Jun · PMID 42380871 · Full text
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, usually diagnosed at late stages, at which point the best option is palliative chemotherapy. Several treatment sequences are currently...
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, usually diagnosed at late stages, at which point the best option is palliative chemotherapy. Several treatment sequences are currently used in the clinic, but the optimal sequence is unknown. METHODS: Retrospectively, 168 PDAC patients treated at a Spanish hospital (single-center study) with either FOLFIRINOX, Gemcitabine (GEM) or Gemcitabine plus nab-paclitaxel (GEM-NABP) as first-line of chemotherapy were studied. Of them, 80 patients received second-line treatment with either GEM- or 5FU-based drugs. Survival analysis was calculated by Kaplan-Meier curves, log-rank test and hazards ratios by univariate and multivariate Cox regression. RESULTS: GEM-NABP and FOLFIRINOX presented similar survival outcomes for first-line treatment, and both were better than GEM alone, although FOLFIRINOX presented higher toxicity than GEM-NABP. However, the best second-line option was application of GEM-based drugs after FOLFIRINOX first-line, which offered a better survival and lower toxicity than 5FU-based treatments after GEM-NABP. Specifically, within the most frequent second-line therapies in our cohort, GEM-NABP outperformed FOLFOX6. Thus, individuals that received FOLFIRINOX followed by GEM-NABP treatment presented better outcomes. CONCLUSIONS: In patients deemed eligible for multiple lines of chemotherapy, initiating treatment with FOLFIRINOX followed by a GEM-NABP regimen may represent a beneficial therapeutic sequence for metastatic PDAC, as opposed to the alternative approach of starting with GEM-NABP followed by a 5FU-based regimen.
Exercise and nutritional prehabilitation in gastrointestinal cancer patients: prospective controlled trial assessing feasibility, safety and effects on quality of life.
Assenbaum L, Pahl A, Baumann FT … +5 more , Weiß C, Bertz H, Seifert G, Neeff H, Greil C
BMC Cancer · 2026 Jun · PMID 42380848 · Full text
BACKGROUND: Perioperative morbidity in gastrointestinal (GI) cancers is closely associated with reduced physical fitness and impaired nutritional status. While prehabilitation has been shown to improve outcomes in patien...
BACKGROUND: Perioperative morbidity in gastrointestinal (GI) cancers is closely associated with reduced physical fitness and impaired nutritional status. While prehabilitation has been shown to improve outcomes in patients with colorectal cancer (CRC), it is not yet standard of care and remains underexplored in other GI malignancies. This study evaluates the feasibility, safety, and preliminary effectiveness of a supervised moderate-to-high intensity exercise program combined with nutritional counseling in a cohort of GI cancer patients scheduled for surgery. METHODS: In a prospective, two-arm, controlled trial, patients scheduled for GI cancer surgery were assigned to a prehabilitation program (2-3 sessions/week ≥ 3 weeks, endurance and resistance training with nutritional counseling) or usual care. Primary endpoints were feasibility (eligibility, recruitment, acceptance, retention, adherence) and safety (adverse events). Secondary endpoint was quality of life (QoL; EORTC QLQ-C30 global score, SF-36 physical and mental health component scores, PCS, MCS), assessed at baseline (t0), presurgery (t1), hospital discharge (t2), and 12-week follow-up (t3). RESULTS: Among the 400 patients assessed for eligibility, 36% met the eligibility criteria. Of those approached, 41% consented to participate, resulting in an overall recruitment rate of 27% (n = 38). Of the recruited patients, 84% completed the study (n = 32; prehabilitation = 17; usual care = 15; mean age 63.5 years, range 38-85; ICD-10 C15-C26). Participants attended 95% of the planned sessions (8.1 ± 3.6) within a mean of 30 days (SD ± 16) and completed 59% at the target intensity. Nutritional counseling was provided to 94% of the patients. No intervention-related serious adverse events occurred. A modest improvement in PCS was observed in the prehabilitation group at t1 (+ 4.25 points), although this finding reached statistical significance only in the one-tailed analysis. No between-group differences were observed for global QoL or MCS. CONCLUSION: Multimodal prehabilitation combining supervised moderate-to-high intensity exercise with nutritional counseling is feasible and safe in a real-world GI cancer population. Recruitment and achievement of prescribed training intensity remain key challenges. Preliminary findings indicate short-term benefits for physical health, supporting further investigations in larger randomized trials. TRIAL REGISTRATION: DRKS00028728; prospectively registered 05/05/2022.
Immune-related adverse events with cancer clinical benefits: a systematic review and meta-analysis.
Li Z, Sun Q, Yang X … +8 more , Ni J, Zhang Y, Wang J, Ding K, Wang G, Yang H, Yu Q, Li Y
BMC Cancer · 2026 Jun · PMID 42380824 · Full text
BACKGROUND: Growing research have reported an association of the occurrence of immune-related adverse events (irAEs) and clinical benefits in patients with immune checkpoint inhibitors (ICIs) treatments, but the findings...
BACKGROUND: Growing research have reported an association of the occurrence of immune-related adverse events (irAEs) and clinical benefits in patients with immune checkpoint inhibitors (ICIs) treatments, but the findings remain controversial. The aim of this study is to identify whether the incidence of irAEs and their subtypes undergoing ICIs treatment is associated with enhanced efficacy and survival benefits in all solid tumors. METHODS: Cochrane Library, Embase, PubMed and Web of Science databases were searched from database inception and December 31, 2023. Two reviewers independently extracted data and reviewed the quality items using the Newcastle-Ottawa Scale criteria, and resolved any discrepancies by consensus discussion with third reviewer. We performed the systematic review and meta-analysis in compliance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis and Meta-analysis of Observational Studies in Epidemiology. The main outcomes were irAEs incidence, objective response rate (ORR), overall survival (OS) and progression-free survival (PFS). Subgroup and sensitivity analyses were performed. RESULTS: A total of 184 articles involving a total of 63,780 patients met the inclusion criteria. The pooled incidence of irAEs in this meta-analysis was 37.3% (95%CI: 34.4%-40.3%). The occurrence of irAEs was associated with increased ORR (RR, 2.32 [95%CI, 2.02-2.67]; I = 80.1%; P < 0.001), and pooled ORRs in irAE+ versus irAE- patients were 39.4% (95%CI: 35.4%-43.5%) versus 16.2% (95%CI: 13.5%-19.4%). Besides, irAEs development presented better weighted average OS (20.03 months versus 10.83 months), and associated with longer OS (HR, 0.55 [95%CI, 0.51-0.59]; I = 70.4%; P < 0.001). Similar finding in PFS, weighted average PFS in irAEs patients was 9.73 months versus 4.15 months in without irAEs patients, and irAEs occurrence improved PFS (HR, 0.58 [95%CI, 0.53-0.63]; I = 50.8%; P < 0.001) compared with those who did not. CONCLUSIONS: The intimate association was observed between the development of irAEs and increased response rate and improved survival benefits in patients who treated with ICIs, and may have useful prognostic value in ICIs therapy.
Comprehensive CYP2D6 genotyping improves phenotype classification and highlights methodological pitfalls in tamoxifen-treated breast cancer.
Alkebbeh L, Berndt A, Oberkanins C … +3 more , Kenj M, Kriegshäuser G, Youssef LA
BMC Cancer · 2026 Jul · PMID 42380819 · Full text
BACKGROUND: The clinical utility of CYP2D6 genotyping in predicting tamoxifen outcomes remains controversial, partly due to incomplete allele coverage and limited assessment of copy number variation (CNV). We aimed to ex...
BACKGROUND: The clinical utility of CYP2D6 genotyping in predicting tamoxifen outcomes remains controversial, partly due to incomplete allele coverage and limited assessment of copy number variation (CNV). We aimed to expand CYP2D6 genetic profiling in Syrian breast cancer patients and to reassess phenotype classification and its clinical relevance. METHODS: In this retrospective cohort of estrogen receptor-positive breast cancer patients treated with adjuvant tamoxifen, CYP2D6 genotyping was performed using a test strip-based assay complemented by semi-quantitative PCR for CNV detection. Selected results were validated by next-generation sequencing (NGS). Diplotypes were translated into activity scores to assign metabolizer phenotypes. Disease-free survival (DFS) was evaluated using time-to-event analyses. RESULTS: Expanded CYP2D6 profiling, incorporating broader allele coverage and CNV analysis, led to metabolizer phenotype reclassification in 19% of patients. NGS identified primer-binding region variants responsible for allele drop-out in conventional assays. No significant association between CYP2D6 phenotype and DFS was observed in the overall cohort. However, exploratory stage-specific analyses suggested shorter DFS among patients with reduced CYP2D6 activity in Stage II disease (HR = 3.59; 95% CI 2.34-67.48), although estimates were imprecise due to small subgroup size. CONCLUSIONS: Comprehensive CYP2D6 profiling improves phenotype assignment and highlights methodological pitfalls that may contribute to inconsistencies in pharmacogenetic studies. While no definitive association with clinical outcomes was observed in the overall cohort, these findings underscore the importance of analytically robust genotyping strategies and warrant validation in larger, prospectively designed cohorts, and highlight the importance of comprehensive genotyping strategies in resolving inconsistencies across pharmacogenetic studies.
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