BMC Cancer[JOURNAL]
Sun
200 papers
Correlated expression of MYBL2 and CCL5 defines an immunosuppressive microenvironment and predicts poor prognosis in intrahepatic cholangiocarcinoma.
Ren J, Xu S, He X … +2 more , Ye H, Li W
BMC Cancer · 2026 Jun · PMID 42310565 · Full text
BACKGROUND: The tumor immune microenvironment critically influences progression and therapeutic response in intrahepatic cholangiocarcinoma (ICC). MYBL2 drives tumor aggressiveness, while CCL5 regulates immune-cell recru...
BACKGROUND: The tumor immune microenvironment critically influences progression and therapeutic response in intrahepatic cholangiocarcinoma (ICC). MYBL2 drives tumor aggressiveness, while CCL5 regulates immune-cell recruitment; however, their combined impact on immune composition and PD-1 therapy response remains undefined. METHODS: Tumor specimens from 127 ICC patients were assessed by immunohistochemistry and whole-slide digital quantification. MYBL2 and CCL5 expression were classified into four combinatorial phenotypes. Associations with immune-cell infiltration, survival, and treatment response were evaluated using correlation analysis, Kaplan-Meier curves, Cox regression, and PD-1 interaction analyses. Seventy patients received adjuvant PD-1 therapy. RESULTS: MYBL2 and CCL5 expression were positively correlated (r = 0.38, p < 0.001). Higher CCL5 levels were associated with increased CD163⁺ TAM density (r = 0.31, p < 0.001) and a reduced CD8/CD163 ratio, indicating an immunosuppressive microenvironment. The MYBL2-CCL5 classification provided clear prognostic discrimination, with the Double-High subgroup showing the shortest OS and PFS. Among PD-1-treated patients, treatment benefit varied markedly across phenotypes: the Double-Low group achieved the greatest survival advantage, whereas the Double-High group showed minimal response, reflecting primary resistance. In multivariable analysis, Double-Low remained strongly protective compared with Double-High. CONCLUSION: The MYBL2-CCL5 co-expression phenotype identifies an immunosuppressive, TAM-dominant microenvironment and serves as a dual biomarker for both prognosis and PD-1 treatment sensitivity in ICC. This immunologic classification offers a practical framework for postoperative risk stratification and personalized immunotherapy decision-making.
Trajectory and predictors of cancer- and treatment-related fatigue (CRF) in adolescent and young adult cancer patients: a prospective, longitudinal study.
Chan A, Chan D, Agrawal P … +5 more , Beppu LL, Kober K, Ng DQ, Sayer M, Trudeau J
BMC Cancer · 2026 Jun · PMID 42304319 · Full text
BACKGROUND: Although cancer- and treatment-related fatigue (CRF) is well recognized as a clinically important and distressing symptom among adolescent and young adult cancer (AYAC) patients, the understanding of the unde...
BACKGROUND: Although cancer- and treatment-related fatigue (CRF) is well recognized as a clinically important and distressing symptom among adolescent and young adult cancer (AYAC) patients, the understanding of the underlying mechanisms behind CRF in AYAC remains limited. We evaluated the trajectory and associated predictors of CRF among AYAC patients (Clinicaltrials.gov: NCT03476070, registered 03/23/2018). METHODS: Newly diagnosed AYAC (15-39 years old) and non-cancer controls (NC) recruited from National Cancer Centre Singapore completed clinical assessments and provided blood draws for inflammatory cytokine measurements every 3 months up to 12 months. Mixed-effects models were used to evaluate significant factors associated with fatigue (MFSI-SF Total score), with AYAC stratified by chemotherapy status (active chemotherapy vs. >30 days post-chemotherapy). RESULTS: Fifty AYAC and 105 NC participants were included, with nearly 1 in 3 AYAC participants reported clinically important CRF at some point. Measurements collected during active chemotherapy had a higher rate of clinically important CRF symptoms relative to samples collected post-chemotherapy and from non-cancer controls. Regression analyses evaluating significant influencers of fatigue scores demonstrated that active chemotherapy, female sex, worsened psychological distress scores, and increased IL-10 levels were associated with worse self-reported fatigue symptoms (all p < 0.05). CONCLUSION: Given the observed prevalence of clinically important CRF amongst AYAC within our study, our results further demonstrate that these patients are vulnerable to fatigue challenges. Identifying factors associated with these debilitating symptoms enables clinicians to better recognize at-risk patients and proactively address symptom burden.
Differential predictive value of inflammation- and coagulation-based composite biomarkers for venous thromboembolism and mortality in patients with NSCLC receiving immune checkpoint inhibitors.
Liu J, Wang L, Xia X … +4 more , Chen S, Yang D, Lu X, Xu Y
BMC Cancer · 2026 Jun · PMID 42304312 · Full text
BACKGROUND: Venous thromboembolism (VTE) is a clinically important complication in patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Although inflammation and coagulation abn...
BACKGROUND: Venous thromboembolism (VTE) is a clinically important complication in patients with non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Although inflammation and coagulation abnormalities may contribute to both thrombosis and poor prognosis, it remains unclear whether routinely available composite biomarkers have similar or differential predictive value for VTE occurrence and all-cause mortality in this setting. METHODS: This single-center retrospective cohort included 206 patients with advanced NSCLC who received at least two cycles of ICI therapy between January 2020 and December 2024. Baseline clinical, treatment, laboratory, and conventional thrombosis risk score data were collected. The D-dimer-to-albumin ratio (DAR), platelet-to-hemoglobin ratio (PHR), and fibrinogen-to-prealbumin ratio (FPR) were analyzed as log2-transformed continuous variables. VTE was evaluated using cumulative incidence functions and Fine-Gray competing-risk models with death without prior VTE as a competing event. All-cause mortality was assessed using time-dependent Cox models, with incident VTE modeled as a time-dependent covariate. Exploratory transition-specific Cox models evaluated baseline-to-VTE, baseline-to-death without prior VTE, and VTE-to-death pathways. E-values and proportional hazards diagnostics were used for sensitivity assessment and model checking. RESULTS: During a median follow-up of 23.0 months, 29 patients (14.1%) developed VTE, 101 died without prior VTE, and 76 were censored. The median time to VTE was 5.0 months, and the 12-, 24-, and 36-month cumulative incidences were 9.2%, 13.7%, and 14.4%, respectively. Neither the Padua nor Khorana score effectively discriminated VTE risk. In Fine-Gray models, DAR was associated with VTE risk after full adjustment, with a subdistribution hazard ratio of 1.28 per doubling (95% confidence interval, 1.00-1.64; P = 0.048), whereas PHR and FPR were not. In time-dependent Cox models, PHR and FPR remained associated with all-cause mortality, whereas DAR and incident VTE did not. Transition-specific analyses suggested that DAR was more closely related to VTE occurrence, whereas PHR and FPR were more closely related to death without prior VTE. CONCLUSIONS: In patients with advanced NSCLC receiving ICIs, DAR, PHR, and FPR showed differential predictive patterns for VTE and all-cause mortality. These findings require validation in larger multicenter cohorts.
Comparative assessment of asparaginase activity, population pharmacokinetics, and safety of biosimilar native Escherichia coli and pegylated asparaginase in children with newly diagnosed acute lymphoblastic leukemia: a pharmacometrics-based randomized clinical trial.
Sethuramalingam S, Mohapatra S, Agarwal PK … +5 more , Kumar-M P, Hota D, Gopal J, Kulkarni A, Srinivasan A
BMC Cancer · 2026 Jun · PMID 42304309 · Full text
BACKGROUND: There is a paucity of data regarding the comparison of asparaginase activity, pharmacokinetics, pharmacodynamic outcomes, and safety of biosimilar native E.coli asparaginase (N-Asp) and biosimilar pegylated a...
BACKGROUND: There is a paucity of data regarding the comparison of asparaginase activity, pharmacokinetics, pharmacodynamic outcomes, and safety of biosimilar native E.coli asparaginase (N-Asp) and biosimilar pegylated asparaginase (P-Asp) used in India. METHODS: A randomized, open-labeled, population pharmacokinetic (PopPK) and pharmacodynamic trial comparing the N-Asp (10,000 IU/m) and P-Asp (1000 IU/m) administered intramuscularly in children with newly diagnosed acute lymphoblastic leukemia. The primary endpoint was asparaginase activity on day 33 of the induction phase of chemotherapy. Population pharmacokinetic modeling was done after the first dose in both groups, and the models were simulated to assess for the subtherapeutic trough concentrations. RESULTS: Fourteen patients were randomized to each arm. The asparaginase activity of 434[interquartile range(IQR) 259, 629] IU/L was observed in the P-Asp compared (p-0.04) to the N-Asp group 64[IQR 27, 184] IU/L on day 33 of the induction phase of chemotherapy. The anti-asparaginase antibody formation, minimal residual disease, and safety were comparable between both groups. The interindividual variability of the population parameters in the PopPK model was higher with N-Asp than P-Asp. The subtherapeutic trough levels of asparaginase were observed more in the N-Asp group (9/14 in N-Asp vs. 0/14 in P-Asp, p < 0.01). CONCLUSION: The asparaginase activity was higher with P-Asp at d33. P-Asp demonstrated less interindividual variability and a predictable kinetic profile, supporting its preferability over N-Asp for first-line management of ALL in the Indian pediatric population. While routine TDM for trough level monitoring may be less critical with P-Asp, TDM retains value to identify silent inactivation, differentiate hypersensitivity from infusion reactions, and confirm adequate activity in high-risk scenarios. In contrast, the higher variability of N-Asp strongly warrants the use of TDM. CLINICAL TRIAL REGISTRATION IDENTIFICATION: CTRI/2019/06/019520 registered on 04/June/2019.
Ultrasonographic characterization of malignant pleural effusion in a murine experimental model.
Mello AJ, Fortunato E, Pereira KR … +5 more , Silva CSR, Sales RKB, Nascimento SCR, Teixeira LR, Acencio MMP
BMC Cancer · 2026 Jun · PMID 42304274 · Full text
BACKGROUND: Malignant pleural effusion (MPE) is a common manifestation of advanced malignancies and is associated with high morbidity and poor prognosis. Thoracic ultrasound (TUS) has emerged as a sensitive, non-invasive...
BACKGROUND: Malignant pleural effusion (MPE) is a common manifestation of advanced malignancies and is associated with high morbidity and poor prognosis. Thoracic ultrasound (TUS) has emerged as a sensitive, non-invasive imaging modality for pleural evaluation; however, standardized ultrasonographic criteria for MPE in murine experimental model remains limited. The aim of this study was to describe and characterize the TUS findings of MPE in an experimental murine model. METHODS: MPE was induced in C57Bl/6 mice by intrapleural injection of Lewis lung carcinoma (LLC) cells. TUS examinations were performed longitudinally at predefined time points to assess pleural fluid depth, pleural line characteristics, pleural thickening, nodules, subpleural consolidations, lung parenchymal alterations, and ultrasound artifacts. Pleural fluid volume, cytology, and histological analyses were obtained after euthanasia and correlated with ultrasonographic findings. RESULTS: TUS detected early pleural changes as early as day 7, preceding large-volume effusion. Pleural fluid depth measured by TUS showed a strong correlation with pleural fluid volume obtained by direct puncture (R = 0.927, p < 0.001). Progressive pleural thickening and nodularity (R = 0.704 e p = 0.002) correlated with histopathological tumor involvement. CONCLUSION: TUS reliably characterizes and quantifies MPE progression in a murine model, closely reproducing human disease patterns. This experimental model supports translational research by enabling longitudinal and non-invasive assessment of biological and pathological processes over time, thereby allowing repeated evaluations within the same subject and significantly reducing the need for animal euthanasia at multiple experimental endpoints, while also providing a robust framework that may corroborate and facilitate future studies in related research fields.
Evolution of treatment patterns and survival outcomes in non-metastatic rectal cancer: a 15-year real-world single-center analysis.
Jang JY, Lim H, Ko J … +8 more , Lee JH, Kim Y, Chi SA, Yoo GS, Park HC, Kim N, Cho YB, Yu JI
BMC Cancer · 2026 Jun · PMID 42304266 · Full text
BACKGROUND: Treatment strategies for rectal adenocarcinoma have undergone substantial evolution, driven by advances in surgical techniques, radiotherapy, and systemic therapies. Nonetheless, longitudinal evidence on thei...
BACKGROUND: Treatment strategies for rectal adenocarcinoma have undergone substantial evolution, driven by advances in surgical techniques, radiotherapy, and systemic therapies. Nonetheless, longitudinal evidence on their real-world adoption and survival trends remains limited. This study investigated temporal trends in patient characteristics, treatment patterns, and outcomes over a 15-year period at a high-volume Korean tertiary center. METHODS: We retrospectively evaluated 6,314 patients with non-metastatic rectal adenocarcinoma who received curative-intent treatment between 2008 and 2022. The study period was divided into five consecutive 3-year intervals to facilitate temporal comparisons. RESULTS: The mean age at diagnosis was 59.4 years, and 62.0% of patients were male. The proportion of clinical T4 tumors increased substantially, from 7.0% to 28.0%, whereas well-differentiated histology declined over time. Minimally invasive surgery rose from 44.5% to 91.0%, driven by the growing adoption of robotic techniques. Neoadjuvant radiotherapy replaced adjuvant radiotherapy as the predominant approach, and capecitabine-based regimens became the most frequent systemic therapy. Across the entire cohort, the 5-year survival rate was 87.6%, with overall survival showing steady improvement across study periods. Relative to the general population, the standardized mortality ratio declined from 5.57 in Period 1 to 3.33 in Period 5, reflecting a measurable reduction in excess mortality. Among patients with locally advanced disease, the highest five-year survival rate was 88.4% in those treated with neoadjuvant therapy followed by surgery. CONCLUSIONS: These findings demonstrate substantial temporal changes in multidisciplinary rectal cancer management, with improved survival observed over time, supporting the continued refinement of multidisciplinary care strategies.
Developing a quality evaluation indicator system for lung cancer diagnosis and treatment: a modified Delphi method study.
Shi L, Fei K, Liu M … +6 more , Zhou C, Yang J, Yang J, Wang J, Wang Z, Yang W
BMC Cancer · 2026 Jun · PMID 42304262 · Full text
OBJECTIVE: To establish a quality evaluation index system for the diagnosis and treatment of lung cancer. METHOD: The Donabedian health assessment model and Delphi method were used to construct an indicator system, and t...
OBJECTIVE: To establish a quality evaluation index system for the diagnosis and treatment of lung cancer. METHOD: The Donabedian health assessment model and Delphi method were used to construct an indicator system, and the Analytic Hierarchy Process was used to determine the weights of each level of indicators. RESULT: The final indicator system constructed includes 3 primary indicators: structure, process and outcome, 15 secondary indicators, and 55 tertiary indicators. Structural indicators include staff, regulations, and facilities; Process indicators include diagnosis, multidisciplinary team (MDT), Neoadjuvant therapy, surgical treatment, adjuvant treatment, radiation therapy, systemic therapy, patient follow-up and patient-centered; Outcome indicators include effectiveness, safety and timeliness. Of the two rounds of Delphi experts consulting, the Expert Enthusiasm Coefficient were respectively 100.0% and 96.15%, the Expert Authority Coefficient were respectively 0.818 and 0.825, and Expert Coordination Coefficient was between 0.476 ~ 0.748. CONCLUSION: The quality evaluation indicator system of lung cancer has high credibility and can be used as a tool for evaluating the quality of lung cancer care.
MRI radiomics and Y PET dosimetry for predicting hepatocellular carcinoma response after radioembolization.
Huang W, Ding J, Yuan H … +3 more , Li Z, Li H, Zeng Y
BMC Cancer · 2026 Jun · PMID 42304258 · Full text
BACKGROUND: To evaluate treatment response in hepatocellular carcinoma (HCC) following Yttrium-90 (Y) radioembolization by integrating pre-treatment contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics with po...
BACKGROUND: To evaluate treatment response in hepatocellular carcinoma (HCC) following Yttrium-90 (Y) radioembolization by integrating pre-treatment contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics with post-treatment Y positron emission tomography (PET) dosimetry. MATERIALS AND METHODS: This retrospective study included 57 patients with pathologically confirmed HCC. All patients underwent CE-MRI within 4-6 weeks before Y transarterial radioembolization (TARE), followed by Y PET/CT within 24 h post-treatment. Tumor response was assessed at three months using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Radiomic features extracted from CE-MRI and 24 h tumor absorbed dose parameters from Y PET/CT were analyzed to predict treatment response, classifying patients as responders or non-responders. RESULTS: Based on mRECIST criteria, 32 patients were classified as responders (all partial response), while 25 were non-responders (20 stable disease, 5 progressive disease). 24-hour average absorbed dose is independent predictive factors for treatment response (OR = 1.06, p = 0.006). The combined model, incorporating clinical characteristics and MRI-derived radiomic features, achieved a sensitivity of 88% (28/32) [95% CI, 71%-96%], specificity of 68% (17/25) [95% CI, 46%-85%], and accuracy of 79% (45/57) [95% CI, 66%-89%]. CONCLUSION: The integration of pre-treatment CE-MRI radiomics with post-treatment Y PET imaging provides complementary insights into tumor biology and therapeutic efficacy. Early tumor absorbed dose metrics derived from Y PET, together with specific CE-MRI radiomic features, show strong correlations with treatment response and may serve as valuable predictive biomarkers to guide patient stratification and optimize radioembolization strategies in HCC.
Clinical profiling of AML1::ETO and KIT exon 17 mutation in pediatric AML by high-throughput drug sensitivity.
Hu Z, Tang X, Chen F … +10 more , Li T, Liu Y, Zhou G, Li Q, Liu S, Wang Y, Wen F, Mai H, Wang L, Liu S
BMC Cancer · 2026 Jun · PMID 42298546 · Full text
BACKGROUND: The favorable prognosis of pediatric AML1::ETO acute myeloid leukemia (AML) is well-established, yet the impact of co-occurring KIT mutations-particularly in exon 17-on clinical outcomes and chemosensitivity...
BACKGROUND: The favorable prognosis of pediatric AML1::ETO acute myeloid leukemia (AML) is well-established, yet the impact of co-occurring KIT mutations-particularly in exon 17-on clinical outcomes and chemosensitivity remains incompletely defined. METHODS: We analyzed the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database comprising 957 pediatric AML patients to assess the clinical characteristics and prognosis of pediatric patients harboring AML1::ETO and KIT mutation using Kaplan-Meier survival analysis and Cox proportional hazards models. Subsequently, we performed experimental validation using bone marrow samples from 16 pediatric AML patients at Shenzhen Children's Hospital by high-throughput drug sensitivity (HDS) screening against therapeutic agents and whole transcriptome sequencing analysis of significant genes. Functional enrichment analysis of these differential expression genes was carried out by Gene Ontology. RESULTS: Analysis from the TARGET database revealed that while AML1::ETO AML generally carries a favorable prognosis, concomitant KIT exon 17 mutations significantly attenuate this survival advantage. Exploratory experimental validation in a limited cohort of AML1::ETO and KIT exon 17 mutation patients suggested a potential trend of broad drug resistance such as cytarabine and daunorubicin. Preliminary transcriptomic analysis identified upregulation of SOCS1, a negative regulator of the JAK-STAT pathway, as a potential feature of this resistant phenotype. Furthermore, elevated SOCS1 expression was associated with poor prognosis. CONCLUSIONS: We conclude that KIT mutations, especially exon 17, confer a high-risk phenotype in otherwise favorable pediatric AML1::ETO AML. Our exploratory data suggest this may be associated with a chemoresistant profile, potentially driven by SOCS1-associated JAK-STAT dysregulation. These findings highlight the necessity of refined risk stratification based on KIT exon profiling and support targeting the SOCS1/JAK-STAT axis to overcome therapy resistance.
Bioinformatics mining and clinical validation of CD274 as a prognostic indicator in hepatocellular carcinoma.
Shi H, Zhang P, Wei Q … +5 more , He H, Wu H, Xiao T, Liu T, Zeng T
BMC Cancer · 2026 Jun · PMID 42298533 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumour with high global incidence and mortality, featuring limited therapeutic options and poor prognosis, which necessitates novel prognostic biomarkers. The imm...
BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumour with high global incidence and mortality, featuring limited therapeutic options and poor prognosis, which necessitates novel prognostic biomarkers. The immune checkpoint molecule CD274 (Programmed Death-Ligand 1, PD-L1) correlates with poor prognosis in most solid tumours, yet its prognostic value in HCC remains controversial, and circulating levels are unclear. This study aimed to multi-dimensionally investigate CD274's expression patterns and clinical significance in HCC. METHODS: Bioinformatics analyses were performed on The cancer genome atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to screen differentially expressed genes, with functional and pathway annotations via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Single-Sample Gene Set Enrichment Analysis (ssGSEA). Survival analysis and univariate/multivariate Cox proportional hazards regression models were used to assess the prognostic value of CD274. PD-L1 protein expression was validated by immunohistochemistry (IHC) on HCC tissue microarrays. Serum PD-L1 concentrations were detected by ELISA in treatment-naive HCC patients and healthy controls. RESULTS: CD274 was lowly expressed in HCC tissues versus normal ones, and its expression correlated with TNF-α/NF-κB, complement, IFN-γ, adipogenesis and oxidative phosphorylation pathways, as well as lymphocyte-mediated immunity, immune globulin complexes and antigen binding. High CD274 expression negatively correlated with Th17 cells but positively with helper T cells, activated dendritic cells (aDCs), Th1 cells, T cells and macrophages via ssGSEA. Patients with high CD274 expression had longer overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI); multivariate Cox regression confirmed CD274 as an independent protective factor for DSS. PD-L1 protein expression showed no significant difference between HCC and normal liver tissues. Serum PD-L1 median was 349.6 pg/mL in HCC patients, significantly higher than 181.3 pg/mL in healthy controls. CONCLUSIONS: This study first identifies a unique "low tissue expression and elevated peripheral blood level" pattern of CD274 in HCC, with intratumoural high expression correlating with favourable prognosis. CD274 may exert distinct roles in local tumour and systemic immune regulation, and serum CD274 is a promising prognostic biomarker for HCC worthy of further research.
Clinicopathological features and immune checkpoint expression patterns in dMMR early gastric cancer: a retrospective pilot study.
Yokotani Y, Sakamoto N, Matsuo M … +8 more , Nakahata Y, Okuyama H, Mukai R, Nagano J, Obora A, Murakami Y, Kojima T, Yagi N
BMC Cancer · 2026 Jun · PMID 42298513 · Full text
BACKGROUND: Although mismatch repair-deficient (dMMR)/microsatellite and instability-high (MSI-H) status is recognized as a biomarker that predicts the efficiency of immune checkpoint inhibitors (ICIs), the efficacy of I...
BACKGROUND: Although mismatch repair-deficient (dMMR)/microsatellite and instability-high (MSI-H) status is recognized as a biomarker that predicts the efficiency of immune checkpoint inhibitors (ICIs), the efficacy of ICIs treatment is still insufficient. Accordingly, insights into the mechanisms of acquired resistance to ICIs in gastrointestinal cancers are necessary, and developing immunotherapeutic strategies to improve response rates is an urgent clinical priority. We investigated the clinical characteristics of dMMR/MSI-H early gastric cancer and analyzed the expression patterns of immune checkpoint molecules within the tumor microenvironment. METHOD: A total of 20 cases of early gastric cancer, treated between November 2019 and July 2024, were included. Immunohistochemistry was performed to assess the expression of mismatch repair (MMR) protein, and patient clinical characteristics were evaluated. Additionally, among the eight cases identified as dMMR early gastric cancer, they were further examined for the expression of immune checkpoint molecules in the tumor microenvironment using immunohistochemical staining. RESULT: The median age of patients diagnosed with dMMR early gastric cancer was 73 years. In 20 patients, female sex and severe atrophy were associated with dMMR status in univariate analysis (OR 7.67, 95% CI 1.04-94.53). The expression pattern of immune checkpoint molecules showed heterogeneity. CONCLUSION: These findings highlight the heterogeneity of immune checkpoint expression patterns and provide preliminary, hypothesis-generating insights into variability in response to PD-1/PD-L1 blockade.
In vitro functional analysis of lysyl oxidase family members in highly metastatic pancreatic cancer cells derived from a syngeneic orthotopic model.
Takahashi-Yamashiro K, Miyauchi K, Shimomura K … +7 more , Nishikawa M, Morishita Y, Nakanishi M, Hayami S, Kawai M, Miyazono K, Ehata S
BMC Cancer · 2026 Jun · PMID 42298507 · Full text
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the highly lethal malignancies, with no established and effective cure. Therefore, identifying novel molecular targets for this cancer remains an urgent prior...
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the highly lethal malignancies, with no established and effective cure. Therefore, identifying novel molecular targets for this cancer remains an urgent priority. METHODS AND RESULTS: We employed a syngeneic orthotopic inoculation model using murine pancreatic cancer Panc02 cells to better recapitulate the pancreatic tumor microenvironment. We established highly metastatic derivatives through three serial transplantation cycles, designated Panc02-3P cells. These cells exhibited enhanced tumorigenicity and metastatic potential both in vitro and in vivo. The RNA-sequence analysis revealed that Panc02-3P cells exhibited mesenchymal-like gene expression changes, compared with parental Panc02 cells, despite no significant changes in EMT-related transcription factor expression. In addition, we found that members of the lysyl oxidase (LOX) family, including LOX, LOXL1, and LOXL3, were markedly upregulated in Panc02-3P cells. The loss-of-function assays using siRNAs targeting LOX and LOXL1 demonstrated that the suppression of these genes significantly attenuated the migratory ability of Panc02-3P cells. CONCLUSION: Collectively, our findings suggest that the LOX family members are associated with the acquisition of a highly migratory and mesenchymal-like phenotype in metastatic pancreatic cancer cells and may contribute to tumor progression.
Feasibility of the effectiveness of a psychoeducational intervention on the physical and psychosexual functioning of women being treated for cervical cancer in a tertiary hospital in Southwest, Nigeria: a quasi-experimental study.
Adebisi TM, Oluwasola TAO, Ndikom CM … +1 more , Salako BL
BMC Cancer · 2026 Jun · PMID 42298499 · Full text
BACKGROUND: Cervical cancer is a global public health concern with significant morbidity and mortality even with advancement in treatment strategies. While efforts have been directed primarily to prevention and eliminati...
BACKGROUND: Cervical cancer is a global public health concern with significant morbidity and mortality even with advancement in treatment strategies. While efforts have been directed primarily to prevention and elimination, there is need to improve the health indices of those who have already been diagnosed. This study was designed to assess the feasibility of the effectiveness of a psycho-educational intervention on the physical and psychosexual functioning as well as health-related quality of life of women with cervical cancer. METHODS: A quasi-experimental single group pre- and post-test design was used to assess the effectiveness of a single-module psychoeducational intervention developed by the researcher through a guide developed for the design of psychoeducational interventions for women with gynaecological cancers. This was carried out among twenty (20) women (> 18years) attending the radiation and clinical oncology unit of Federal Medical Centre, Abeokuta, Nigeria. Women's functioning levels were assessed using two (2) standardized tools at baseline and four (4) weeks after the intervention. Data was analyzed with SPSS version 26 and hypotheses were tested using Wilcoxon Signed Rank test at a significance level of ≥ 0.05. RESULT: 60% were between 46 to 56years with a mean age of 51.7 ± 7.6; 70% were Yoruba, 45% were married and a higher percentage (35%) were traders. None of the respondents was ever vaccinated against Human Papilloma Virus and were on chemotherapy. Only 45% had partner support and 5 to 6 children with majority (55%) being post-menopausal. The intervention showed evidence of clinical relevance for all domains but did not yield a statistical significance for the physical (d=-0.016, p=0.954), psychological (d=-0.015, p=0.678) and sexual functioning (d=-0.098, p=0.678). However, HRQoL was significant (d=-0.702, p=0.011). Pain and partner support were the most significant socio-economic predictors of quality of life. CONCLUSIONS: Psychoeducational intervention can help improve the physical and psychosexual domains of functioning as well as the health-related quality of life of women with cervical carcinoma.
Identification and validation of programmed cell death-related genes in osteosarcoma: inhibiting CIB1 as a promising therapeutic strategy.
Hu B, Du L, Lu C … +6 more , Huang D, Pan M, Xue F, Shen Y, Ding L, Yin N
BMC Cancer · 2026 Jun · PMID 42298489 · Full text
BACKGROUND: This study explores programmed cell death (PCD)-related genes in osteosarcoma through bioinformatics and experimental validation. METHODS: Analysis of datasets from the GEO and TCGA databases identified 5,327...
BACKGROUND: This study explores programmed cell death (PCD)-related genes in osteosarcoma through bioinformatics and experimental validation. METHODS: Analysis of datasets from the GEO and TCGA databases identified 5,327 differentially expressed genes (DEGs), among which 294 overlapped with PCD-related genes. RESULTS: LASSO regression analysis identified six hub genes, and five of these (CIB1, CREB3L1, IL6R, TGFβ2, and TNFRSF10C) were further validated in osteosarcoma tissues. Notably, CIB1 exhibited significantly elevated expression and was selected for in-depth analysis. CIB1 downregulation inhibited osteosarcoma cell proliferation and invasion by inducing apoptosis and causing G2/M phase cell cycle arrest, and was associated with increased p53 expression, decreased phosphorylation of Akt and STAT3, and altered BCL2/BAX ratios, suggesting involvement of these pathways in the observed effects. CONCLUSIONS: In vitro experiments confirmed the tumor-suppressive role of CIB1 inhibition. These findings highlight CIB1 as a promising therapeutic target for osteosarcoma treatment.
Psychometric properties of patient-reported outcome measures for health-related quality of life in multiple myeloma: a systematic review based on COSMIN guidelines.
Xie L, Feng Q, Wang J … +3 more , Qin W, Ding Y, Wu Z
BMC Cancer · 2026 Jun · PMID 42298481 · Full text
PURPOSE: To systematically identify patient-reported outcome measures (PROMs) used to assess health-related quality of life (HRQoL), symptoms, and disease burden in patients with multiple myeloma (MM), and to appraise th...
PURPOSE: To systematically identify patient-reported outcome measures (PROMs) used to assess health-related quality of life (HRQoL), symptoms, and disease burden in patients with multiple myeloma (MM), and to appraise their measurement properties using the COSMIN methodology. METHODS: A systematic review was conducted in accordance with the COSMIN guideline for reviews of PROMs. Eligible studies reported PROM development, content validation, cross-cultural adaptation, or one or more measurement properties of PROMs used in adult patients with MM. Methodological quality was assessed using the COSMIN Risk of Bias checklist. The results for each measurement property were rated against the COSMIN criteria for good measurement properties, and the certainty of evidence was graded using the modified GRADE approach recommended by COSMIN. RESULTS: Twenty-six studies involving 14 PROMs were included. The EORTC QLQ-MY20 was the most frequently evaluated MM-specific module, followed by MyPOS, HM-PRO, MDASI-MM, FACT-MM, MySIm-Q, and QLICP-MM. Evidence was most often available for internal consistency, structural validity, and hypothesis testing for construct validity. By contrast, formal evidence on measurement error, criterion validity, and cross-cultural validity was seldom reported. No PROM demonstrated uniformly high-quality evidence across all key measurement properties. The EORTC QLQ-MY20 and MyPOS showed the broadest body of supportive evidence and appear to be the most defensible options for MM-specific HRQoL assessment, although additional high-quality content validity and longitudinal measurement studies remain necessary. CONCLUSION: Current evidence supports the use of several MM-specific PROMs, particularly the EORTC QLQ-MY20 and MyPOS, but the overall evidence base remains uneven. Future research should prioritize patient-centered content validation, measurement-error evidence, cross-cultural validity, responsiveness, and interpretability to strengthen PROM selection for MM clinical trials and practice.
Distinct epidemiologic patterns of mesothelioma: evidence from a 16-year provincial cohort in China.
Yin S, Hu T, Li X … +2 more , Xu D, Shu Y
BMC Cancer · 2026 Jun · PMID 42298472 · Full text
BACKGROUND: Epidemiologic data on mesothelioma in China remain limited, particularly with respect to long-term, province-level characterization of demographic features and survival outcomes. METHODS: We conducted a 16-ye...
BACKGROUND: Epidemiologic data on mesothelioma in China remain limited, particularly with respect to long-term, province-level characterization of demographic features and survival outcomes. METHODS: We conducted a 16-year retrospective cohort study of mesothelioma patients diagnosed at a major provincial tertiary referral center in China between 2009 and 2025. Among 128 identified cases, 93 met strict pathological criteria and were included for analysis. We evaluated sex distribution, anatomic site, age at diagnosis, and survival outcomes, and compared these features with representative cohorts from the United States, Europe, and Japan. RESULTS: Our 16-year provincial cohort showed a nearly equal male-to-female ratio that markedly distinct from the male predominance reported in Western populations. Peritoneal mesothelioma accounted for 33.3% of cases, a proportion higher than that typically reported in global cohorts. The higher proportion of female patients was observed across both pleural and peritoneal mesothelioma. The median age at diagnosis was significantly younger than that observed in the United States. The median progression-free survival (PFS) and overall survival (OS) were 10 months and 16 months, with a notable survival advantage for females with peritoneal mesothelioma. Notably, only 7.5% of patients had documented asbestos exposure, indicating additional environmental and/or genetic contributors maybe relevant in this setting. CONCLUSIONS: This long-term provincial cohort delineates mesothelioma epidemiology at the province level in China, marked by a near-equal sex distribution with substantial female representation across disease subtypes, a high proportion of peritoneal cases, younger age at diagnosis and a low prevalence of documented asbestos exposure. These findings show clear region-specific evidence, underscoring potential geographic heterogeneity in mesothelioma epidemiology.
Sex differences in gastric cancer mutational burden reflect MLH1-associated epigenetic regulation.
Klein N, Shweiki D
BMC Cancer · 2026 Jun · PMID 42289660 · Full text
BACKGROUND: Tumor mutational burden (TMB) is widely used as a biomarker for predicting response to immune checkpoint inhibitors. Therefore, understanding its variability across patient groups, particularly between sexes,...
BACKGROUND: Tumor mutational burden (TMB) is widely used as a biomarker for predicting response to immune checkpoint inhibitors. Therefore, understanding its variability across patient groups, particularly between sexes, and its underlying biological determinants is of critical importance. METHODS: We analyzed autosomal TMB and its association with DNA repair-related regulatory mechanisms in gastric cancer across TCGA-STAD and independent targeted sequencing cohorts. Sex-stratified analyses were integrated with gene expression, promoter methylation, and regression modeling. RESULTS: Female tumors exhibited significantly higher autosomal TMB compared with male tumors, with differences most pronounced in older female patients. Across tumors, TMB was strongly associated with reduced MLH1 expression and increased MLH1 promoter methylation, while female tumors exhibited significantly higher MLH1 methylation levels. These relationships are consistent with mismatch repair deficiency as a major driver of mutation accumulation. In multivariable regression models adjusting for MLH1 methylation and expression, the association between sex and TMB was attenuated, suggesting that MLH1-related processes contribute to the observed sex differences. Subtype-aware analyses further suggested that the female-associated TMB elevation was partly related to increased representation of MSI/MMR-deficient tumors among females, while female and male MSI tumors showed comparable TMB. Independent targeted sequencing cohorts showed consistent directional trends, although these did not reach statistical significance. CONCLUSIONS: Together, our findings indicate that sex differences in mutation burden are linked to MLH1-associated epigenetic regulation, mismatch repair deficiency, and MSI/MMR-deficient tumor biology. These results highlight the importance of incorporating sex-specific molecular context into the interpretation of genomic biomarkers and support a more refined, biologically informed approach to precision oncology.
Strategies for enhancing participation of underrepresented patient populations in cancer clinical trials: learning from "bright spots".
Miller JE, Schwartz J, Ramachandran R … +2 more , Ross J, Suttiratana SC
BMC Cancer · 2026 Jun · PMID 42288829 · Full text
BACKGROUND: Adequate participation of women, older adults, racial and ethnic subgroups, and other groups, in pivotal trials for cancer therapies is critical for understanding and trusting the safety and efficacy of new m...
BACKGROUND: Adequate participation of women, older adults, racial and ethnic subgroups, and other groups, in pivotal trials for cancer therapies is critical for understanding and trusting the safety and efficacy of new medical products across populations. Despite consensus on the importance of representative research and extensive documentation of trial participation barriers, progress has been minimal for most groups, raising the question: What more can be done to enhance participation of underrepresented patient populations in cancer clinical trials, and in turn, improve medical evidence? METHODS: We used a "bright spot" approach to understand what drives successful representation of Black and LatinX patients in cancer clinical trials. We conducted 1-h interviews with "bright spot trial" teams, teams who conducted trials that adequately enrolled Black or LatinX patients relative to disease burden among pivotal trials supporting FDA approval of novel cancer therapeutics between 2012 and 2021, to identify organizational contexts and facilitators associated with success across multiple action levels. Transcripts were analyzed using constant comparative methods. RESULTS: Thirteen participants from 8 bright spot trial teams described a coherent set of strategies associated with representative enrollment, clustering across five levels: patient and community, clinician, trial and site, sponsor organization, and policy. Key practices included prospective budgeting for mitigating participant expenses; patient- and community co-developed educational programs; navigator use; early clinician engagement and referral training; protocol simplification, decentralization, and broadening of eligibility criteria; expansion into community and satellite hospitals affiliated with NCI Designated Cancer Center trial sites; and sustained, non-transactional community partnerships. At the organizational level, "bright spot trial" teams emphasized the importance of executive leadership commitment, real-time dashboarding on enrollment goals, performance-based incentives, employee training, and minimizing reliance on generic vendor solutions. CONCLUSIONS: Sponsors that achieved representative enrollment in oncology trials shared a common operational playbook: reduce patient and site burden, expand access to where care is delivered, widen trial eligibility, invest in trusted relationships, and embed accountability through leadership, data and incentives. Translating these strategies from bright spots into standard practice, supported by clearer regulatory guidance and evaluation, offers a concrete path toward more accessible and generalizable cancer clinical research.
The predictive role of tertiary lymphoid structures in the prognosis and response to immunotherapy of bladder cancer patients: a systematic review and meta-analysis.
Hu P, Wang C, Zeng X … +7 more , Jin S, Huang J, Wang Q, Li X, Du Y, Song Y, Xu T
BMC Cancer · 2026 Jun · PMID 42288780 · Full text
BACKGROUND: The association between tertiary lymphoid structures (TLS) and clinical outcomes in bladder cancer (BCa) patients, particularly their value in predicting immunotherapy response, remains inconsistent and has n...
BACKGROUND: The association between tertiary lymphoid structures (TLS) and clinical outcomes in bladder cancer (BCa) patients, particularly their value in predicting immunotherapy response, remains inconsistent and has not been systematically evaluated. OBJECTIVE: This systematic review and meta-analysis aimed to: (1) evaluate the association between TLS and survival outcomes in BCa; (2) examine the relationship between TLS and clinicopathological characteristics; and (3) summarize evidence on TLS and immunotherapy response. METHODS: We systematically searched PubMed, Embase, and Web of Science from inception to February 1, 2026. Hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) were extracted and pooled. The study protocol was registered with PROSPERO (CRD420261282595). RESULTS: Eight studies involving 1706 patients were included in the quantitative synthesis. Pooled analysis revealed that high TLS levels were significantly associated with improved OS (HR = 0.49, 95% CI: 0.33-0.74), PFS (HR = 0.51, 95% CI: 0.45-0.58), and DFS (HR = 0.42, 95% CI: 0.22-0.79). TLS showed a significant correlation only with tumor multiplicity among various clinicopathological features. Qualitative synthesis of six studies suggested that while baseline TLS had limited predictive value for immunotherapy response, therapy-induced increases in TLS number, density, and maturation were consistently associated with favorable treatment outcomes. CONCLUSION: High TLS levels are associated with favorable survival outcomes in bladder cancer patients, supporting their role as a prognostic biomarker. Therapy-induced TLS dynamics, rather than baseline status alone, may be a more relevant predictive biomarker for immunotherapy efficacy. These findings warrant validation in larger, prospective studies.
Correction: A Randomized clinical trial evaluating the impact on survival and quality of life of 177Lutetium[Lu]-edotreotide versus everolimus in patients with neuroendocrine tumors of the lung and thymus: the LEVEL study (GETNE T-2217).
Capdevila J, Pubul V, Anido U … +32 more , Walter T, Molina-Cerrillo J, Alonso-Gordoa T, Garcia-Carbonero R, San-Roman-Gil M, Llana B, Jimenez-Fonseca P, Viñuales MB, Ansquer C, Baudin E, Lepage C, Del Olmo-García M, Ruffinelli JC, Beron A, Haissaguerre M, Deshayes E, Taïeb D, Baldari S, Sansovini M, Cingarlini S, Filice A, Panzuto F, Álvarez-Álvarez R, Lousberg L, Nana FA, Hernando J, García-Álvarez A, García-Burillo A, Villacampa G, Vandamme T, Fazio N, Durand A
BMC Cancer · 2026 Jun · PMID 42288752 · Full text
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