Cancer[JOURNAL]
Sun
200 papers
Factors associated with quality of work life among colorectal cancer survivors: a cross-sectional study after returning to work.
Li Z, Cao J, Chen S … +3 more , Chai G, Dong Y, Chen L
BMC Cancer · 2026 Jun · PMID 42332647 · Full text
BACKGROUND: To facilitate the vocational rehabilitation of colorectal cancer patients, more information is needed on the influencing factors related to the quality of work life of colorectal cancer patients after their r...
BACKGROUND: To facilitate the vocational rehabilitation of colorectal cancer patients, more information is needed on the influencing factors related to the quality of work life of colorectal cancer patients after their return to work. This study examines the Quality of Working Life (QWL) among the patients with colorectal cancer (CRC) survivors after returning to work and identifies influencing factors. METHODS: A cross-sectional study from January to May 2023 followed 290 CRC survivors from a Chinese hospital's oncology outpatient department. The General Questionnaire, Quality of Working Life Questionnaire for Cancer Survivors (QWLQ-CS), Simplified Coping Style Questionnaire, and the Social Support Revalued Scale were used for data collection. Descriptive statistics, T-tests, ANOVA, correlation, and multiple linear regression analyses were conducted with the Statistical Package for the Social Science (SPSS) version 25.0. RESULTS: The QWL score of CRC survivors was (67.72 ± 12.21). Factors such as the per capita monthly family income, medical payment method as self-employment, basic medical insurance system for urban residents, stoma status, positive coping strategies, passive coping strategies, and social support utilization emerged as significant QWL determinants, while passive coping strategies was inversely related to QWL. CONCLUSION: CRC survivors have greater room for improvement in their work life (QWL) after returning to work. To enhance their reintegration and QWL, healthcare professionals should implement individualized interventions that reflect the various challenges these individuals face. It is important to provide special attention to colorectal cancer survivors who pay for their medical care directly, have residential health insurance, have an ostomy, or have a per capita family income of less than 281⁄ per month, as they tend to report worse levels of quality of work life. Clinical personnel should rapidly detect these risk factors and offer the required assistance and resources to ensure that these patients are adequately prepared to resume employment and enhance their overall quality of work life.
Long-term cardiovascular risk in survivors of hematologic malignancies: a meta-analysis.
Liu S, Liu S, Hu Y … +3 more , Deng J, Sun G, Fang X
BMC Cancer · 2026 Jun · PMID 42332608 · Full text
BACKGROUND: The survival rate for hematologic malignancies is steadily improving. With the encouraging trend and the aging of these survivors, there is an ever-increasing responsibility for identifying adverse cardiovasc...
BACKGROUND: The survival rate for hematologic malignancies is steadily improving. With the encouraging trend and the aging of these survivors, there is an ever-increasing responsibility for identifying adverse cardiovascular outcomes associated with carcinogenesis and/or anti-cancer therapies across the span of their lives. However, prospective studies have yielded inconsistent results. METHODS: We performed a meta-analysis to summarize the evidence regarding the association between leukemia, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in relation to later risk of cardiovascular disease (CVD). Relevant literatures were identified from PubMed and Web of Science databases through May 2024 and reviewing reference lists of retrieved articles. RESULTS: From the 2412 studies screened, we included 50 studies with 550,385 participants, spanning 1940-2020 for leukemia and 1940-2016 for both Hodgkin and non-Hodgkin lymphoma. The pooled fully adjusted RRs of total CVD, ischemic heart disease (IHD), heart failure (HF), and stroke associated with leukemia were 2.68 (95% confidence interval: 2.22-3.25), 1.46 (1.25-1.70), 4.13 (2.41-7.06), and 3.05 (2.16-4.32), respectively. For HL or NHL survivors, similar positive associations were observed in our study. In addition, compared with survivors with chemotherapy (2.12; 1.89-2.38), radiotherapy-treated survivors had a greater risk of CVD (4.06; 2.84-5.81). CONCLUSIONS: In summary, survivors of hematologic malignancies, especially those who receive radiotherapy, are at highest risk of developing CVD, emphasizing the need for targeted prevention strategies.
Is active surveillance of CIN2 always appropriate? Clinical outcomes and factors associated with progression and regression over 48 months in an HPV-positive cohort.
Bruno MT, Pagana A, Aiello T … +5 more , Pivetti E, Cavallaro AG, Tarascio M, Panella MM, Valenti G
BMC Cancer · 2026 Jun · PMID 42332606 · Full text
BACKGROUND: Active surveillance of cervical intraepithelial neoplasia grade 2 (CIN2) is increasingly adopted to reduce the risk of overtreatment, particularly in young women. However, the appropriateness of this approach...
BACKGROUND: Active surveillance of cervical intraepithelial neoplasia grade 2 (CIN2) is increasingly adopted to reduce the risk of overtreatment, particularly in young women. However, the appropriateness of this approach remains debated, especially in light of evidence suggesting an increased long-term risk of cervical cancer in certain subpopulations. METHODS: A retrospective cohort study was conducted on HPV-positive women with histologically confirmed p16-positive CIN2 managed with active surveillance. Medium-term clinical outcomes included regression, persistence, and progression to CIN3 or higher during follow-up. Survival analyses (Kaplan-Meier), Cox regression models, and Modified Poisson regression models with robust standard errors were performed to identify independent factors associated with progression. The mean follow-up was 27 months, with a maximum follow-up of 48 months. RESULTS: During the observation period, spontaneous regression was observed in 61% of cases, while 25.5% of patients showed progression and 13.8% persistence of the lesion. Regression occurred predominantly within the first 24-36 months, followed by a plateau in the curves. Progression was significantly associated with high-grade cytology (ASC-H/HSIL) and HPV16/18 positivity. In multivariable models, both factors remained independent factors associated with progression, whereas non-16/18 HPV genotypes and low-grade cytology were associated with a higher likelihood of regression. CONCLUSIONS: Although this study does not allow for a direct assessment of long-term cancer risk, the identification of early factors associated with persistence and progression provides clinically relevant insights into CIN2 profiles associated with an increased risk of progression within the observed follow-up period. These findings suggest that active surveillance of CIN2 may not be equally appropriate across all patient subgroups and requires careful risk stratification based on virological and cytological factors to support selective and clinically sound management.
PET/CT Radiomics-based assessment of tumor heterogeneity for predicting immunotherapy outcomes in advanced lung squamous cell carcinoma: a retrospective prognostic modeling study.
Zhang R, Li Y, Duan F … +4 more , Wang X, Zhang M, Li P, Wang D
BMC Cancer · 2026 Jun · PMID 42332591 · Full text
BACKGROUND: Accurately predicting progression-free survival (PFS) in patients with advanced lung squamous cell carcinoma (LUSC) receiving immunotherapy remains a clinical challenge. Radiomics has emerged as a promising n...
BACKGROUND: Accurately predicting progression-free survival (PFS) in patients with advanced lung squamous cell carcinoma (LUSC) receiving immunotherapy remains a clinical challenge. Radiomics has emerged as a promising non-invasive approach; however, its application in this specific patient population remains relatively limited. METHODS: A total of 129 patients were retrospectively enrolled. Radiomics features were extracted from baseline positron emission tomography/computed tomography (PET/CT) images. Feature reproducibility was evaluated using intraclass correlation coefficients (ICC), and only features with ICC > 0.75, indicating good reproducibility, were retained. A three-step feature selection strategy, including univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox modeling, was applied to construct the radiomics signature. Model performance was evaluated using time-dependent receiver operating characteristic (ROC) analysis, Kaplan-Meier survival analysis, and bootstrap resampling. Additionally, a 3D convolutional neural network (CNN) model was explored for comparative analysis. RESULTS: The final model achieved a 2-year AUC of 0.673. The relatively stable AUC values across time points (1-year: 0.670; 2-year: 0.673; 3-year: 0.651) suggest that the model primarily captures baseline risk stratification rather than strong time-dependent variation. Patients in the high-risk group exhibited a significantly increased risk of progression compared with those in the low-risk group (HR = 4.36, 95% CI: 2.70-7.04, P < 0.001). The radiomics signature remained an independent predictor of PFS in multivariate analysis. In comparison, the 3D CNN model demonstrated inferior predictive performance compared with the radiomics-based model. CONCLUSION: The PET/CT-based radiomics model enables non-invasive risk stratification of patients with advanced LUSC receiving immunotherapy and may provide complementary information for clinical decision-making.
Demographic, birth, parental characteristics, and the risk of early-onset colorectal cancer: A population-based nested case-control study in California.
Siddique S, Wang R, Berardi D … +4 more , Johnson CH, Wiemels JL, Metayer C, Ma X
Cancer · 2026 Jul · PMID 42324895 · Full text
BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before the age of 50 years, has been increasing. The relationship between demographic, birth, and parental charac...
BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before the age of 50 years, has been increasing. The relationship between demographic, birth, and parental characteristics and risk of EOCRC has not been elucidated. METHODS: This study included 1221 cases born and diagnosed with EOCRC at the age of 0 to 39 years in California during 1988 through 2021 and 61,050 frequency-matched controls based on birth year. Odds ratios (OR) and 95% CIs were estimated using multivariable logistic regression models. RESULTS: Based on multivariable analysis, males had 34% higher risk of EOCRC compared to females (OR = 1.34; 95% CI, 1.20-1.51), and Hispanic ethnicity was associated with 43% higher risk of EOCRC (OR for Hispanic versus non-Hispanic White = 1.34; 95% CI, 1.20-1.51). Having a foreign-born mother was associated with a lower risk of EOCRC (OR = 0.85; 95% CI, 0.73-0.97). Among females, every 500-g increase in birthweight was associated with 10% increase in EOCRC risk (OR = 1.10; 95% CI, 1.01-1.21) and having a father aged ≥35 years was associated with higher risk of EOCRC (OR = 1.56; 95% CI, 1.08-2.25). No other demographic, birth, and parental characteristic was significantly associated with risk of EOCRC. CONCLUSION: High birthweight, male sex, Hispanic ethnicity, and older paternal age are potential risk factors for EOCRC. Maternal birthplace, which is associated with diet, smoking patterns, other health-promoting characteristics, may be protective against EOCRC. These factors require future research for validation and evaluation of possible mechanisms.
Factors influencing delay to diagnosis and treatment among pediatric oncology patients at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: a cross-sectional survey.
Bipsue AK, Asfaw HM, Yusuf NT
BMC Cancer · 2026 Jun · PMID 42324508 · Full text
BACKGROUND: Childhood cancer represents a significant cause of morbidity and mortality among children under 15 years of age and is a growing public health concern, particularly in low- and middle-income countries, includ...
BACKGROUND: Childhood cancer represents a significant cause of morbidity and mortality among children under 15 years of age and is a growing public health concern, particularly in low- and middle-income countries, including Ethiopia. OBJECTIVE: The purpose of this study was to assess factors Influencing delay to diagnosis and treatment initiation among pediatric cancer patients attending at Tikur Anbessa Specialized Hospital oncology unit in Addis Abeba, Ethiopia, in 2019. METHODS: An institutional-based cross-sectional study involving 244 pediatric cancer patients was conducted between February and April of 2019. Data were collected from parents/caregivers using a structured questionnaire through face-to-face interviews and supported by review of medical records. Bivariate and multivariate analyses with adjusted odds ratios were employed to evaluate the association between dependent and independent factors. Statistical analysis was performed using STATA (Version 14) with a significance level of P < 0.05. RESULT: A total of 244 children participated, with an average age of 6.4 (± SD 3.2 years). One hundred twenty-seven (52.0%) were reported as patient delays (> 30 days), while 179 (73%) were reported as health system delays. Children aged 5-9 years AOR:2.98; 95% CI,1.35, 6.57; three times delayed than children 0-4 years; where as children from rural areas AOR:2.28; 95% CI, 1.07, 4.88; were about 2.28 delayed as compared to children who come from urban. Furthermore, parents of children who visited traditional healers AOR: 7.85, 95% CI; 3.88,15.89 were more likely to be delayed as compared to their counter's parts. Health system-related factors, such as lack of medical insurance AOR: 5.52, 95%CI: 2.61, 11.69 and first visit to a health institution AOR: 16.13, 95%CI: 4.00, 65.03, were identified as the cause of delay. CONCLUSION AND RECOMMENDATIONS: In conclusion, prolonged patient and health system delays were significantly associated with age AOR: 2.98; 95% CI: 1.35-6.57), rural residence AOR: 2.28; 95% CI: 1.07-4.88, use of traditional healers AOR: 7.85; 95% CI: 3.88-15.89), low disease awareness, and lack of health insurance at diagnosis (AOR = 5.52; 95% CI: 2.61-11.69). To reduce delays, targeted health education for parents and healthcare providers, improved early detection and referral systems, strengthened multisectoral collaboration, expansion and decentralization of pediatrics oncology care facilities and further qualitative research to explore underlying causes of delay are recommended.
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.
Patient-reported outcomes in castration-resistant prostate cancer with bone metastases treated with radium-223 with or without olaparib.
McKay RR, Xie W, Ajmera A … +9 more , Araneta A, Folefac E, Hussain A, Kyriakopoulos CE, Olson A, Parikh M, Parikh R, Saraiya B, Shapiro GI
Cancer · 2026 Jul · PMID 42319132 · Full text
BACKGROUND: The combination of olaparib plus radium-223 improved progression-free survival in patients with metastatic castration-resistant prostate cancer with bone metastases (BM) in the multicenter, randomized, phase...
BACKGROUND: The combination of olaparib plus radium-223 improved progression-free survival in patients with metastatic castration-resistant prostate cancer with bone metastases (BM) in the multicenter, randomized, phase 2 COMRADE trial (NCT03317391). Here, the patient-reported outcome (PRO) analysis of this trial is reported. METHODS: Patients were randomized 1:1 to olaparib plus radium-223 (arm A) or radium-223 alone (arm B). PROs were assessed via the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory (BPI) at baseline and every 12 weeks. Clinically meaningful changes were defined as a ≥10-point change in FACT-P total score and a ≥30% or ≥2-point change in BPI score. Mixed-effects analysis-of-covariance models assessed PRO changes with adjustment for baseline characteristics among patients with baseline and ≥1 postbaseline assessment within 24 weeks. RESULTS: Of 114 treated patients, 74 (65%) were evaluable (arm A, n = 40; arm B, n = 34). Baseline characteristics were balanced, with a median age of 70-72 years and Eastern Cooperative Oncology Group performance status of 1 in 60%-62%, prior docetaxel in 50%-55%, >20 BM in 45%-47%, and pain medication use in 60%-72% of patients. No significant differences in FACT-P total score change was observed at Week 12 (-4.87; 95% CI, -13.4 to 3.62) or Week 24 (1.79; 95% CI, -8.28 to 11.9). BPI pain severity did not differ at Week 12 (0.44; 95% CI, -0.44 to 1.33) or Week 24 (-0.20; 95% CI, -1.32 to 0.93). Arm B showed greater improvement in BPI pain interference at Week 12 (1.09; 95% CI, 0.14 to 2.05), which was not sustained at Week 24. CONCLUSIONS: The addition of olaparib to radium-223 was not associated with significant detriment to PROs or pain, which supports the tolerability of this combination.
Magnetic resonance imaging-targeted biopsy with index lesion ipsilateral or bilateral systematic biopsy in prostate cancer: A multicenter, paired, noninferiority, observational trial.
Cheng Y, Huang H, Wang M … +9 more , Zhu L, Peng S, Li D, Marra G, Qi R, Ding X, Liu M, Qiu X, Guo H
Cancer · 2026 Jul · PMID 42319125 · Publisher ↗
BACKGROUND: Index lesion-focused ipsilateral systematic biopsy (iSB) has been proposed as a core-reduction alternative to MRI-targeted biopsy combined with systematic biopsy (TB + SB) for prostate cancer, but prospective...
BACKGROUND: Index lesion-focused ipsilateral systematic biopsy (iSB) has been proposed as a core-reduction alternative to MRI-targeted biopsy combined with systematic biopsy (TB + SB) for prostate cancer, but prospective multicenter validation is limited. METHODS: This prospective multicenter trial (NCT06584279) enrolled biopsy-naive men with Prostate Imaging Reporting and Data System (PI-RADS) ≥4 lesions or PI-RADS 3 plus prostate-specific antigen (PSA) density ≥0.15 ng/mL/cm. All underwent MRI-targeted biopsy (≥2 cores/lesion) with 12-core SB. Through core-level reclassification, the authors simulated TB + iSB (targeted biopsy combined with index lesion-ipsilateral systematic biopsy). The primary outcome was cancer detection rate (CDR) of clinically significant prostate cancer (csPCa; Grade Group ≥2) with a noninferiority margin of -3%. Secondary outcomes included clinically insignificant prostate cancer (cisPCa; Grade Group 1) detection and pathological concordance after radical prostatectomy. RESULTS: Among 564 men (median age, 69 years; median PSA, 7.3 ng/mL), TB + iSB demonstrated a noninferior csPCa CDR versus TB + SB (40.78% vs. 42.38%; difference, -1.6 percentage points; 95% CI, -2.69 to -0.50), with the lower bound above the -3% noninferiority margin. The cisPCa CDR was slightly lower with TB + iSB than with TB + SB (13.83% vs. 14.36%; difference, -0.53 percentage points; 95% CI, -2.01 to 0.92). Among 189 surgical patients, pathological concordance was similar, whereas upgrading was numerically more frequent and downgrading numerically less frequent under simulated TB + iSB. CONCLUSIONS: TB + iSB met the prespecified noninferiority criterion for csPCa detection relative to TB + SB and may represent a promising core-reduction strategy in transperineal MRI-guided biopsy, although the full protocol still provided additional contralateral information.
Selinexor in combination with azacitidine or ruxolitinib in myelodysplastic/myeloproliferative neoplasm overlap syndromes: A multicenter prospective study.
Lin X, Liu Z, Yang C … +8 more , Zhuang J, Wei N, Cui T, Zheng W, Ye F, Ding X, Chen M, Han B
Cancer · 2026 Jul · PMID 42318939 · Publisher ↗
BACKGROUND: Therapeutic strategies for myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs) remain suboptimal. Selinexor, an oral selective inhibitor of exportin 1, represents a mechanism-based therapeutic ap...
BACKGROUND: Therapeutic strategies for myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPNs) remain suboptimal. Selinexor, an oral selective inhibitor of exportin 1, represents a mechanism-based therapeutic approach. Preclinical and clinical evidence indicated synergistic antileukemic effects when selinexor was combined with hypomethylating agents or janus kinase inhibitors. METHODS: A prospective, single-arm trial was conducted to evaluate selinexor plus either azacitidine (for MDS-dominant features) or ruxolitinib (for MPN-dominant features) in patients with MDS/MPN. The primary end point was the overall response rate at 6 months, which was assessed according to 2015 International Working Group criteria. Secondary end points included safety, progression, and survival. RESULTS: Twenty patients were enrolled (four with MDS-dominant features, 16 with MPN-dominant features). The median age was 66 years in the MDS group and 62.5 years in the MPN group. The overall response rate was 60% (12 of 20 patients; 95% confidence interval [CI], 36.1%-80.5%) overall, 75% (three of four patients; 95% CI, 31.1%-95.4%) in the MDS group, and 56.3% (nine of 16 patients; 95% CI, 33.2%-76.9%) in the MPN group. In the MDS group, clinical benefits included improvements in the total symptom score, erythroid response, platelet response, and spleen response (one in each of four patients; 25% for each response). In the MPN group, partial responses occurred in two of 16 patients (12.5%), and partial bone marrow responses occurred in three of 16 (18.8%), with additional benefits including spleen response (five of 16; 31.3%), total symptom score improvement (two of 16; 12.5%), erythroid response (two of 16; 12.5%), and platelet response (one of 16; 6.3%). Adverse events occurred in 14 patients (70%). Three patients experienced grade 3 or greater events, including two disease-related fatalities. After a median follow-up of 6 months (range, 2-15 months), one patient's disease transformed to acute myeloid leukemia. CONCLUSIONS: Selinexor combined with azacitidine or ruxolitinib showed encouraging efficacy with a manageable safety profile in patients with MDS/MPN.
MASAI trial results support larger scale use of AI-supported mammography.
Lawrence L
Cancer · 2026 Jun · PMID 42316764 · Publisher ↗
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