Abstract Background This study examined the associations of estimated glucose disposal rate (eGDR), a surrogate of insulin sensitivity, and the insulin resistance indices TG/HDL-C and TyG with gastrointestinal (GI) cancer mortality in the UK Biobank. Methods We included 369,447 participants without cancer at baseline and recorded 4,305 GI cancer-related deaths over a mean follow-up of 13.5 years. Fine-Gray models assessed associations of eGDR, TG/HDL-C, and TyG with GI cancer mortality. Results Higher eGDR was associated with lower pooled GI cancer mortality (sHR, 0.67; 95% CI, 0.61–0.74; P < 0.001); associations with EC, ESCC, CRC, LC, and PC mortality remained significant after false discovery rate (FDR) correction. TyG, but not TG/HDL-C, remained associated with pooled GI cancer mortality, and both markers remained associated with LC mortality. Subgroup analyses were exploratory. Conclusions Higher eGDR was associated with lower pooled and several site-specific GI cancer mortality outcomes, whereas TG/HDL-C and TyG associations were modest and site-specific. These findings do not establish clinical utility.
Breast cancer progression is influenced not only by tumor-intrinsic alterations but also by interactions within the tumor immune microenvironment (TIME). We aimed to identify genetically regulated susceptibility genes associated with immune-related cellular states in breast cancer. We first performed a transcriptome-wide association study (TWAS) using FinnGen summary statistics to identify candidate genetically regulated genes associated with breast cancer susceptibility. Their transcriptional activity was subsequently mapped onto the GSE176078 single-cell atlas using AUCell, UCell, and AddModuleScore. Because B cells consistently showed the highest enrichment, we further applied hdWGCNA to characterize co-expression modules associated with the high TWAS score (HTS) state. We then integrated LASSO, Random Forest, Boruta, and XGBoost analyses to prioritize candidate hub genes. The prognostic and immunological relevance of ELF1 was further evaluated in GSE96058 (n = 3,273) and METABRIC (n = 2,509). Functional validation was further performed using ELF1-modulated B-cell models, including Raji and GM12878 cells, together with direct co-culture assays with MDA-MB-231 breast cancer cells. TWAS analysis identified 65 candidate genetically regulated genes, and their activity appeared to be preferentially enriched in B cells. hdWGCNA further linked HTS-associated modules to RNA splicing and B-cell activation pathways. Among the candidate genes, ELF1 was the only candidate feature consistently prioritized across all four machine learning algorithms. Low ELF1 expression was associated with inferior overall survival in the GSE96058 cohort, while a consistent survival trend was observed in the METABRIC cohort. ELF1 expression positively correlated with naive B-cell infiltration but showed negative correlations with plasma cells and M0/M1 macrophages. Functional experiments demonstrated that ELF1 modulation affected B-cell proliferation, activation marker expression, RNA splicing-related molecules, and altered the proliferative and invasive behaviors of breast cancer cells in direct co-culture systems. By integrating TWAS, single-cell transcriptomics, machine learning, and preliminary experimental validation, we identified ELF1 as a B-cell-associated prognostic biomarker in breast cancer. These findings suggest that ELF1 may represent a molecular link between genetically regulated expression patterns and B-cell-related immune states within the tumor microenvironment.
Invasive non-mucinous lung adenocarcinoma (INMA) is biologically heterogeneous, with histological patterns defining distinct subtypes; however, the significance of non-predominant components is not fully characterized. We investigated the associations of micropapillary/solid (MP/S) and lepidic (Lep) components with clinicopathological features, molecular profiles, and perioperative circulating tumor DNA (ctDNA) dynamics in a Chinese cohort. We retrospectively analyzed 73 INMA patients with definitive histological subtyping and next-generation sequencing data. Tumors were assessed for MP/S and Lep components irrespective of predominance. Histologic patterns were correlated with clinicopathological variables, genomic alterations, and individualized tumor-informed ctDNA detection. The cohort was predominantly early-stage, with 71.2
Cancer of unknown primary (CUP) is defined by the presence of metastatic disease without an identified primary tumor despite comprehensive diagnostics. The absence of a known primary tumor creates substantial diagnostic uncertainty for patients and caregivers, and precludes site-specific, evidence-based treatments. Fibroblast activation protein inhibitor (FAPI) PET tracers have recently gained attention as promising alternatives to [18F]fluoro-2-deoxy-d-glucose ([18F]FDG), as they selectively target cancer-associated fibroblasts within the tumor microenvironment and demonstrate low physiological uptake in normal tissues. This favorable biodistribution yields high tumor-to-background contrast, potentially overcoming the limitations of [¹⁸F]FDG and enhancing diagnostic performance in patients with CUP. This investigator-initiated, patient advocacy supported, multicenter, prospective clinical trial evaluates the diagnostic performance of the novel radiotracer [¹⁸F]F-FAPI for primary tumor detection in patients with CUP. Fifty patients (aged ≥ 18 year) diagnosed with CUP after a standard diagnostic work-up, including [18F]FDG PET-CT, will be recruited in six medical centers throughout the Netherlands. Participation in the study involves a single [¹⁸F]F-FAPI PET-CT scan. Images will be centrally interpreted by two independent nuclear medicine physicians or nuclear radiologists, with a consensus report and recommendations provided to the treating physician. A central Truth Panel of multidisciplinary experts will review all pseudonymized clinical data collected up to six months after the [¹⁸F]F-FAPI PET-CT, including whole genome sequencing, pathology, and additional imaging, to assess the clinical impact and added diagnostic value of [¹⁸F]F-FAPI PET-CT. Patient recruitment commenced in July 2024. The study will be completed after the six-month follow-up of the last enrolled participant has been completed. This study aims to determine the utility of [¹⁸F]F-FAPI PET-CT in identifying the primary tumor in CUP patients with inconclusive results from conventional diagnostics, including [¹⁸F]FDG PET-CT. We hypothesize that [¹⁸F]F-FAPI PET-CT will identify the primary tumor in at least 15
Advances in precision oncology and cancer therapies have improved survival for Canadians with advanced cancer, resulting in a growing population living long-term while receiving ongoing treatment. However, little is known about their supportive care needs or how they differ from those treated with curative intent, limiting the relevance of existing resources. As such, this study aimed to explore the lived experiences and challenges faced by Canadians receiving ongoing treatment for advanced cancer. A qualitative study was conducted involving semi-structured virtual interviews with 22 Canadians receiving ongoing treatment for advanced cancer. Interviews were audio-recorded, transcribed verbatim, and analysed thematically using descriptive techniques. Two overarching themes were identified. First, participants described challenges unique to living long-term with advanced cancer, including persistent treatment-related symptoms, uncertainty about the future, and disruptions to daily routines, responsibilities, and identity. Second, participants described barriers and facilitators influencing their ability to live well with advanced cancer, including capacity for self-management and self-advocacy, support from family and friends, financial considerations, and support from healthcare providers. Participants reported difficulty navigating available resources and limited guidance from providers and felt that existing supports and resources were insufficient to address the challenges they experienced. Individuals living with advanced cancer face physical, emotional, practical, and adjustment-related challenges that are distinct from those with earlier stage cancers. Existing supports are rarely effective at addressing these challenges, leaving patients to grapple with unmet needs. Future research should include the development and adaptation of supports that are accessible and tailored to this population.
Adult-type diffuse gliomas, central nervous system (CNS) World Health Organization (WHO) grade 4 (CNS WHO grade 4), remain the most aggressive primary malignant brain tumors despite advances in multimodal treatment. We evaluated overall survival and factors associated with mortality among adults with WHO grade 4 diffuse gliomas treated at two tertiary neurosurgical referral centers in the Democratic Republic of the Congo (DRC). We conducted a multicenter retrospective cohort study including 102 adults with histologically confirmed CNS WHO grade 4 gliomas treated between January 2018 and December 2025. Demographic, clinical, surgical, pathological, treatment, and available molecular characteristics were extracted from institutional records. Overall survival was estimated using the Kaplan–Meier method. Factors associated with mortality were evaluated using multivariable Cox proportional hazards regression adjusted. Among the 102 patients included, the median age was 50.0 years (interquartile range [IQR], 41.2–57.0), and 64 (62.7
Postoperative complications are common after major cancer surgeries, occurring in 25–50
SMARCA4-deficient thoracic tumor(SMARCA4-DT) is a relatively rare and highly aggressive tumors, typically associated with mutations or deletions of the SMARCA4 gene. This article aims to explore the clinical features of SMARCA4-DT patients, disease outcomes, effective prognostic indicators, and the therapeutic value of immune checkpoint inhibitors (ICIs) in advanced SMARCA4-DT patients. A total of 98 cases of SMARCA4-DTs diagnosed at Shanghai Chest Hospital from May 2019 to September 2023 were selected and collected.The clinical features of all patients were analyzed, and disease-free survival (DFS) and overall survival (OS) were assessed for those with complete surgical resection. For advanced, non-resectable patients, treatment strategies were divided into a chemotherapy group and a combination therapy group, including ICIs. A statistical analysis of progression-free survival (PFS) and OS was performed to explore the therapeutic role of ICIs in advanced patients and to identify potential predictive markers. Among the 98 patients, 60 (61.2
Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide. Postoperative radiotherapy (PORT) ± chemotherapy improves outcomes in patients with high- and intermediate-risk pathologic features but is associated with substantial morbidity. While de-escalation strategies have been explored mainly in HPV-positive oropharyngeal cancer, prospective evidence across broader HNSCC populations is lacking. Retrospective evidence suggests that a pathology-driven, tailored PORT strategy may safely reduce treatment volumes while maintaining acceptable oncologic control. This trial prospectively evaluates the safety and efficacy of compartmentalized PORT (COMPORT) of the four most common HNSCC localizations. COMPORT is a multicenter, single-arm phase II trial with Bayesian design that will enroll 50 patients with resected oral cavity, oropharynx, larynx, and hypopharynx HNSCC and an indication for adjuvant PORT, as recommended by a multidisciplinary tumor board. Eligible patients will be treated according to a COMPORT-specific algorithm, omitting low-risk anatomical compartments. In some cases, this results in complete omission of PORT. Primary endpoint is the rate of recurrence in omitted (non-irradiated) compartments within 30 months. Secondary endpoints include loco-regional control, progression-free survival, overall survival, physician-rated toxicity (TAME score), and quality of life (MDADI, EORTC QLQ-C30 and HN43). In this trial, COMPORT will be considered successful if the probability that recurrence rates remain below 18
To evaluate the clinical significance of folate receptor alpha (FRα) expression in endometrial serous carcinoma. We retrospectively analyzed 47 patients with histopathologically confirmed endometrial serous carcinoma who underwent hysterectomy and received systemic therapy. FRα expression was assessed by immunohistochemistry and categorized as high or low based on ≥ 25
To systematically explore the effects of clinicopathological characteristics on lymph node metastasis (LNM) and long-term overall survival (OS) in cervical squamous cell carcinoma patients, and to further identify risk factors for high-level and multiple lymph node metastases. A total of 788 patients who underwent surgical treatment for cervical squamous cell carcinoma between June 2012 and March 2019 were retrospectively included. Stratified Cox proportional hazards regression models stratified by pathological grade were constructed to screen independent prognostic factors for OS and address minor proportional hazards assumption violation. Restricted cubic spline (RCS) binary logistic regression and conventional multivariable logistic regression were performed to evaluate independent predictors of overall lymph node metastasis, high-level (common iliac artery and above) lymph node metastasis, and three or more metastatic lymph nodes (gLNM3). Increased tumor volume (HR = 1.006, P = 0.007), positive lymphovascular space invasion (LVSI, HR = 1.961, P < 0.001), positive vaginal invasion (HR = 1.753, P = 0.001), and positive lymph node metastasis (HR = 2.938, P < 0.001) were confirmed as independent adverse prognostic factors for OS. No postoperative adjuvant treatment modality significantly affected patient survival. RCS logistic regression revealed a marginally significant overall association between continuous tumor volume and lymph node metastasis (global P = 0.053), with a positive linear risk trend observed within the tumor volume range of 10–35 cm³ (OR = 1.866, P = 0.040). Multivariable logistic regression identified LVSI positivity (OR = 4.276, P < 0.001), pathological grade III (OR = 1.706, P = 0.002), endogenic tumor growth pattern (OR = 2.676, P = 0.008), and mass-type gross tumor (OR = 6.455, P = 0.016) as independent risk factors for lymph node metastasis. Among patients with pelvic lymph node metastasis, tumor maximum diameter > 4 cm (OR = 2.290, P = 0.027) and positive LVSI (OR = 3.889, P < 0.001) were independent predictors of high-level lymph node metastasis. Furthermore, LVSI positivity independently increased the risk of having ≥ 3 metastatic lymph nodes (OR = 2.195, P = 0.005). Tumor volume, LVSI, vaginal invasion, and lymph node metastasis are robust independent prognostic indicators for overall survival in cervical squamous cell carcinoma patients. LVSI serves as a core risk factor that comprehensively promotes overall, high-level, and multiple lymph node metastases. Tumor volume exhibits a marginal linear predictive effect on lymph node metastasis, while adjuvant treatment shows no significant impact on patient long-term survival.
Although differentiated thyroid carcinoma (DTC) generally has a favorable prognosis, a subset of patients develop aggressive disease associated with poor outcomes. Current risk stratification relies mainly on clinicopathological features, whereas circulating inflammatory and immune biomarkers may provide complementary prognostic information. This study aimed to evaluate the prognostic significance of systemic inflammatory status, thyroid-related biomarkers, and peripheral immune profiles in patients with DTC. We retrospectively analyzed 430 patients with pathologically confirmed DTC who underwent surgical resection. Preoperative inflammatory markers, thyroid-related biomarkers, and peripheral immune cell profiles were evaluated, and their associations with overall survival (OS) were assessed using Kaplan–Meier analysis and Cox proportional hazards regression models. Compared with healthy controls and patients with benign thyroid nodules, patients with DTC exhibited significantly elevated levels of the systemic immune-inflammation index (SII), thyroglobulin (Tg), and thyroglobulin antibody (TgAb) (all P < 0.001). Higher levels of SII, Tg, and TgAb were associated with lymph node metastasis and distant metastasis. Multivariable Cox regression analysis identified older age, follicular thyroid carcinoma, lymph node metastasis, distant metastasis, elevated SII, increased Tg and TgAb levels, and higher CD8⁺ T-cell proportion as independent predictors of inferior OS. Kaplan–Meier analyses further demonstrated that higher proportions of CD3+, CD4+, and CD19 + cells and lower proportions of CD56 + cells were associated with improved OS, whereas CD127 + cell proportion showed no significant association with OS. Systemic inflammatory status, thyroid-related biomarkers, and peripheral immune cell profiles provide complementary prognostic information in patients with DTC. Integration of SII, Tg/TgAb levels, and immune profiling may complement existing risk stratification approaches and facilitate individualized postoperative risk assessment and surveillance.
To develop and validate an interpretable machine learning (ML) model based on CT radiomics to predict the 2-year disease-free survival (DFS) in muscle invasive bladder cancer (MIBC) patients with multicenter validation. A total of 377 patients with MIBC who underwent radical cystectomy were included from five institutions between November 2012 and February 2022. Of these, 264 patients were assigned to the training set, and 113 to the test set. The least absolute shrinkage and selection operator (LASSO) regression was used to select radiomics features and construct radiomics score (Rad-score). Five common ML models were developed by combining the Rad-score with significant clinicopathologic factors. The shapley additive explanation (SHAP) method was employed to visualize the prediction process. The Rad-score was constructed by eleven radiomics features, achieving AUCs of 0.827 and 0.771 in predicting 2-year DFS in the training and test sets, respectively. Kaplan–Meier survival analysis showed significant differences in DFS between the high-risk and low-risk groups stratified by the Rad-score in both the training (hazard ratio: 5.40[95
Multicentric lower genital tract intraepithelial neoplasia involves multiple intraepithelial lesions in the vagina, cervix, and vulva and is commonly associated with persistent high-risk human papillomavirus infection. Despite improved cervical lesion screening, understanding of vulvovaginal lesions remains limited. Patients with cervical lesions often have concurrent vulvar and/or vaginal intraepithelial neoplasia, and these concurrent lesions may be overlooked without multisite assessment. To characterize the clinical features and identify factors associated with cervicovaginal-vulvar multicentric intraepithelial neoplasia and to explore the apparent performance of multivariable models in distinguishing multicentric from isolated cervical lesions. We conducted a retrospective, single-center, case-control study of 362 patients with histologically confirmed cervical lesions and concurrent vaginal and/or vulvar lesions identified during the same diagnostic episode, and 391 patients with isolated cervical lesions. Clinical and colposcopic characteristics were compared, and independent associations were assessed using multivariable logistic regression. Apparent model performance was assessed using receiver operating characteristic, calibration, and decision curve analyses. Concurrent high-grade vaginal and vulvar lesions were significantly more common among patients with high-grade than among those with low-grade cervical lesions (vaginal high-grade squamous intraepithelial lesions: 34.75
Non-invasive biomarkers can inform prostate cancer diagnosis, surgical decision-making, and treatment. However, early screening biomarkers, including prostate-specific antigen (PSA), lack specificity due to elevation in benign conditions. Thymidine kinase 1 (TK1), a DNA synthesis enzyme, is a serum-based marker of cellular proliferation. We performed a meta-analysis to evaluate whether TK1 distinguishes prostate cancer from non-malignant states and reflects tumor aggressiveness. Literature searches in PubMed, Scopus, and Embase identified studies reporting serum TK1 concentrations in prostate cancer. Meta-analysis using RevMan compared TK1 levels across prostate cancer, no evidence of malignancy (NOMA), and healthy controls using standardized mean differences (SMDs). Associations with tumor aggressiveness were assessed by Gleason score (GS) (≤ 6, 7, ≥ 8) and by comparing SMDs, area under the curve (AUC), and correlations for TK1 versus PSA. Eight studies including 868 patients with prostate cancer, 320 with NOMA, and 900 healthy controls were analyzed. TK1 was significantly elevated in prostate cancer compared to both healthy controls [SMD: 1.51 95
Accumulating evidence indicates that pan-apoptosis plays a significant role in tumour progression, highlighting the importance of determining its relevance to tumour prognosis and treatment. This study aims to classify the molecular patterns of pan-apoptosis and explore the molecular and tumour microenvironment characteristics to predict the prognosis of prostate cancer. Prostate cancer samples were clustered into two subtypes based on the expression matrix of pan-apoptosis-related genes. Pan-apoptosis-related genes were identified using differential gene expression analysis. A novel model was developed incorporating the four core genes. Validation of the model was conducted through EdU assays, quantitative real-time PCR, and Western blotting. The pan-apoptosis model was successfully developed, demonstrating robust performance in prognostic prediction. Notably, the low PANS group exhibited higher TIDE scores than the high PANS group, suggesting a potentially less favorable response to immune checkpoint blockade therapy in the low-PANS population. Furthermore, our study revealed that HLTF was highly expressed in PRAD cell. Meanwhile, the function of HLTF in PRAD has been explored and the results showed the proliferation capacity of PRAD cell diminished following the knockdown of HLTF. Furthermore, our study uncovered a potential mechanistic link, suggesting that HLTF may regulate PANoptosis through the modulation of ZBP1-PANoptosome assembly. Molecular docking analysis identified several compounds and drugs that target HLTF. Among them, the small-molecule compound EGCG was found to interact with the HLTF protein and effectively reverse the enhanced proliferative capacity of prostate adenocarcinoma (PRAD) induced by HLTF overexpression. Our study investigated the mechanism of action of PANoptosis and emphasised its potential clinical applications. The PANoptosis model could accurately predict the prognosis of patients with PRAD and guide the treatment. HLTF could regulate the assembly of ZBP1-PANoptosome, thereby influencing the proliferation of prostate cancer cells. Additionally, EGCG and other HLTF-binding compounds merit further preclinical evaluation as potential therapeutic leads.
Colorectal cancer (CRC) is a significant contributor to cancer mortality in sub-Saharan Africa, yet it remains understudied. This study describes care gaps and survival outcomes of CRC in Rwanda. This was a retrospective observational cohort study. We included patients treated at Butaro Cancer Center of Excellence, a tertiary cancer center in Northern Rwanda. 163 patients with CRC who presented between July 2012 and June 2018 were included. Comprehensive data were collected on patient characteristics; diagnostic workup; treatment gaps; and survival outcomes up to August 2023. The main outcome measures were five-year overall survival (OS) for the entire cohort, and disease-free survival (DFS) for patients with localized disease; these were estimated using the Kaplan-Meier method. Exploratory multivariate survival analysis examined the associations between patient/disease characteristics and survival. The cohort median age was 53 years; 86 (53
Primary gastrointestinal lymphoma (PGIL) comprises histologically diverse extranodal lymphomas with markedly different biological characteristics and clinical outcomes. This study evaluated the association between pretreatment serum cytokine concentrations and clinical outcomes in PGIL, with particular attention to interleukin-10 (IL-10). We retrospectively reviewed 165 adults with PGIL treated between 2012 and 2022. Pretreatment serum cytokine measurements were available for 85 patients, who comprised the cytokine cohort. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Serum IL-10 was analyzed as a log-transformed continuous covariate in Cox proportional-hazards models. Conventional receiver operating characteristic (ROC) analysis of vital status was performed as an exploratory assessment of discrimination for overall mortality. Histology-stratified IL-10 distributions, a DLBCL-specific continuous Cox analysis, and a sensitivity analysis excluding MALT and follicular lymphoma were also performed. In the full cohort, the reverse Kaplan–Meier median follow-up was 33.4 months, and the 3-year OS rate was 85.1
Most patients with ovarian cancer are diagnosed at an advanced stage, when adequate solid tumor tissue for molecular testing is frequently unavailable. Malignant ascites is a common complication at this stage and represents an abundant, easily accessible source of tumor cells. We evaluated whether ascites-derived paraffin-embedded cell blocks can support both immunohistochemical (IHC) diagnosis and detection of homologous recombination repair (HRR) gene mutations. Paraffin-embedded cell blocks were prepared from the ascitic fluid of 58 patients with ovarian cancer treated between January 2016 and June 2021. Diagnostic IHC markers (Pax-8, WT-1, CA-125, CK7 and CK20) were assessed, and mutations in 32 genes (including 13 genetic and therapy related genes, 19 homologous recombination repair (HRR) genes) were detected by next-generation sequencing (NGS) technology. Germline and somatic BRCA1/2 status was determined by comparison with matched blood samples. Across histological subtypes, Pax-8 (87.5–100
