DNA methylation is an emerging biomarker for cervical cancer screening. This study aimed to evaluate the diagnostic performance of paired box gene 1/junctional adhesion molecule 3 (JAM3) dual-gene methylation analysis for detecting high-grade cervical intraepithelial neoplasia and cervical cancer, and to explore its potential utility as a triage biomarker for high-risk human papillomavirus positive women.

A systematic search was conducted across 5 databases, including PubMed, for studies on PAX1/JAM3 methylation testing in cervical cancer screening. Following quality assessment via the QUADAS-2 tool, statistical analyses were performed using Meta-Disc 1.4 and Stata 17 software.

Eight studies involving 7494 participants were included in the meta-analysis. For diagnosing cervical intraepithelial neoplasia grade 2 and above the pooled sensitivity was 0.81 (95% CI: 0.73-0.88), specificity was 0.95 (95% CI: 0.94-0.96), and the area under the curve was 0.96. For diagnosing cervical intraepithelial neoplasia grade 3 and above the pooled sensitivity was 0.85 (95% CI: 0.75-0.92), specificity was 0.88 (95% CI: 0.86-0.89), and the area under the curve was 0.90.

PAX1/JAM3 dual-gene methylation testing demonstrates high diagnostic accuracy for detecting high-grade cervical intraepithelial neoplasia and cervical cancer, supporting its potential role as a triage biomarker in high-risk human papillomavirus positive women.

Gastric cancer remains a leading gastrointestinal malignancy with persistently high incidence and poor prognosis. Marital status, an established proxy for social support, has been linked to survival in several solid tumors, yet its impact on gastric-cancer outcomes remains uncertain in large contemporary cohorts. The aim of this study was to quantify the association between marital status and cancer-specific and overall survival in patients with gastric cancer in a large, contemporary, population-based cohort, and to determine whether marital status serves as an an independent prognostic factor for gastric-cancer outcomes. Using the surveillance, epidemiology, and end results database, we identified patients with primary gastric adenocarcinoma diagnosed from 2013 through 2022. Patients were dichotomized as married or unmarried. Baseline characteristics were compared with χ2 tests. To mitigate selection bias, 1:1 propensity-score matching (PSM) was performed. Cancer-specific survival (CSS) and overall survival (OS) were estimated with Kaplan-Meier and log-rank tests. Subgroup analyses and multivariable Cox regression were conducted to determine the independent prognostic value of marital status. A total of 39,013 patients were included (median follow-up 14 months). Before PSM, unmarried patients had significantly worse CSS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.14-1.20, P < .001) and OS (HR 1.20, 95% CI 1.16-1.23, P < .001). After 1:1 PSM (15,256/group), the survival gap narrowed but remained significant (CSS: HR 1.12, P < .001; OS: HR 1.15, P < .001). Subgroup analyses showed unmarried status was consistently associated with poorer CSS and OS across most strata. Multivariable Cox regression confirmed unmarried status as an independent adverse prognostic factor for both CSS (HR 1.17, 95% CI 1.13-1.20, P < .001) and OS (HR 1.19, 95% CI 1.15-1.22, P < .001). In this large population-based cohort, unmarried status was independently associated with worse gastric-cancer outcomes. Marital status is a readily available marker of social and economic support that identifies patients at higher risk of adverse outcomes; these patients may benefit from targeted psychosocial, financial, and logistical support during and after treatment.

To determine the cost-effectiveness of molecular testing for indeterminate (Bethesda III/IV) thyroid nodules in a real-world, single-payer healthcare system.

This retrospective population-based cohort study analyzed fine-needle aspiration biopsy (FNAB) and lobectomy data for thyroid nodules in Manitoba, Canada, during 2023. Microcosting was performed to capture surgical, surveillance, molecular testing, and complication costs in 2023 Canadian dollars. Six molecular tests (Afirma, ThyroSeqV3, ThyroidPrint, ThyroSPEC, ThyGeNEXT/ThyraMIR, and mir-THYpe) were evaluated using site-specific malignancy prevalence (21%) and published test statistics.

The study was performed within a publicly funded healthcare system.

Participants were 18 years and above having undergone FNAB in Manitoba.Intervention or Exposures:Three scenarios were identified Current Care, Molecular Testing, and Reference Standard (diagnostic lobectomy) pathways. The total cost per year were compared among scenarios.

Cost-utility analyses compared Current Care, Molecular Testing, and Reference Standard pathways. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. A $50 000/QALY willingness-to-pay (WTP) threshold was used to interpret ICERs.

Among 1486 FNABs performed, 413 were indeterminate nodules, and 149 patients underwent diagnostic lobectomy. The cost of lobectomy was $7542.69 per patient. All molecular testing strategies improved net QALYs and demonstrated ICERs ranging from $9791.03 to $58 749.94 per QALY compared to Current Care. All tests apart from Afirma were cost-effective at the WTP threshold relative to Current Care. Compared to the Reference Standard, all molecular testing strategies were dominant.

For the investigated Manitoba scenario, molecular testing for indeterminate thyroid nodules can be a cost-effective strategy, possibly reducing unnecessary surgeries while preserving patient outcomes.

This study contributes to the body of evidence suggesting molecular testing is cost-effective and has potential to influence political decisions in health care spending.

Breast cancer incidence varies by race, stage at diagnosis, and molecular subtype. However, these patterns are often obscured in overall estimates, particularly in high-burden settings. This study examined incidence trends overall and by race, stage at diagnosis, and molecular subtype among women in Mississippi.

We used population-based data from the Mississippi Cancer Registry, including Black and White women aged ≥ 18 years diagnosed with primary breast cancer from 2010 to 2019. Age-adjusted incidence rates (IRs) per 100,000 population were standardized to the 2000 United States standard population. Trends were assessed using Joinpoint regression estimating average annual percent changes (AAPCs) and annual percent changes (APCs). Multivariable Poisson regression estimated incidence rate ratios (IRRs) with 95% confidence intervals (CIs).

Among 21,130 women (64.4% White; 35.6% Black), the overall age-adjusted IR was 166.0 per 100,000 with no significant change over time (AAPC = 0.48%; 95% CI: -0.27 to 1.24). Black women had higher incidence than White women (178.0 vs. 159.1). Among White women, incidence increased modestly (AAPC = 0.60%; 95% CI: 0.06-1.13). Trends among Black women were not significant overall (AAPC = 0.36%; 95% CI: -0.25 to 1.04) but increased from 2014 to 2019 (APC = 1.95%; 95% CI: 0.77-4.26) after an initial decline. Localized-stage incidence increased in both groups, while Black women had higher regional- and distant-stage incidence. In adjusted models, Black women had higher incidence of HER2-overexpressing (IRR = 1.55; 95% CI: 1.15-2.10) and triple-negative cancer (IRR = 2.35; 95% CI: 1.74-3.17) than White women.

Overall incidence remained stable, but substantial heterogeneity across subgroups underscores the need for stratified surveillance and equity-focused cancer control strategies in high-burden settings.

Pancreatic cancer (PC) disrupts metabolic and nutritional processes, including glucose homeostasis and albumin levels. Both hyperglycemia and hypoalbuminemia have been linked to poorer outcomes in various cancers, including PC. This study investigates the preoperative glucose-to-albumin ratio (GAR) as a potential prognostic marker of overall survival in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma (PDAC).

This single-center retrospective analysis included patients who underwent curative-intent pancreatectomy for PDAC and adenosquamous carcinoma of the pancreas between 2017 and 2024. GAR was calculated from preoperative laboratory tests. Kaplan-Meier and Cox regression analyses were performed for recurrence-free and overall survival.

A total of 566 patients were included (51% males and 49% females, mean age 68.3); 548 had PDAC and 18 had adenosquamous carcinoma of the pancreas. High GAR was associated with elevated CA 19-9, CEA and BMI (p < 0.0001, p < 0.0001, p = 0.02, respectively), more advanced T staging (p = 0.001), increased tumor size (p = 0.007), and AJCC staging (p = 0.04), as well as perineural invasion (p = 0.01) and lymphovascular invasion (p = 0.008). Kaplan-Meier analysis demonstrated significantly worse overall survival in high GAR patients (26.6 vs. 35.0 months, p = 0.004), while low albumin was associated with significantly worse recurrence-free survival (15.5 vs. 20.7 months, p = 0.04). Cox regression identified high GAR (HR = 1.3, p = 0.04), lower BMI (Body Mass Index) (p = 0.02), higher CA 19-9 (p = 0.006), N staging (p = 0.002), histological tumor grading (p < 0.0001), neoadjuvant chemotherapy (p = 0.002) and perineural invasion (p = 0.03) as independent risk factors for poorer overall survival.

Higher preoperative GAR is associated with more advanced disease at presentation and an adverse prognosis in patients with resected PC.

The generation and maintenance of effective tumor-specific CTL responses require more than antigen recognition. In most settings, TCR engagement must be accompanied by co-stimulatory input, with the B7-1/B7-2-CD28 axis being one of the best-characterized examples. When this second signal is weak or absent, tumor-reactive CD8+ T cells may recognize tumor antigens but fail to expand, survive, or acquire and sustain cytotoxic activity. Tumors take advantage of this vulnerability by reducing co-stimulatory ligand availability, increasing inhibitory checkpoint signaling, and remodeling the tumor microenvironment in ways that further restrict T-cell activation. Depending on the stage and context of dysfunction, this shift may favor anergy-like dysfunction, impaired persistence and apoptotic attrition, or, under persistent antigen exposure and sustained inhibitory signaling, exhaustion-associated dysfunction, thereby promoting immune escape. This review examines how reduced or functionally restricted B7-CD28 co-stimulation impairs CTL activation, intratumoral reactivation, and persistence, and how checkpoint signaling, suppressive immune cells, metabolic stress, and stromal barriers compound this defect within tumors. We also evaluate strategies intended to restore or bypass inadequate co-stimulatory input, distinguishing established checkpoint-based interventions from co-stimulatory agonists, engineered T-cell therapies, multispecific antibodies, and gene-based approaches that remain preclinical or early translational in many settings. We propose that mechanism-matched therapy should be guided by the phase at which the dominant barrier arises-tumor-reactive CD8+ T-cell priming, intratumoral CTL reactivation, or long-term CTL persistence.

Cancer-associated fibroblasts (CAFs) are pivotal stromal component in tumor microenvironment (TME) and participate in regulating tumor development and progression via exosomes (exos) mediated intercommunication. However, the intricate mechanism underlying the exosomal miRNAs from CAFs in gastric cancer (GC) tumorigenesis remains ambiguous. Herein, we found that miR-4435 was highly expressed in both CAFs- derived exos and GC tissues and was associated with TNM stage as well as tumor size in GC patients. Additionally, inhibition of miR-4435 remarkably restricted GC proliferation, migration, and invasion in vitro and in vivo; whereas facilitating ferroptosis in GC cells. Moreover, miR-4435 could bind with the downstream target NDUFA10 mRNA and was shown to silence NDUFA10 expression. Importantly, exosomal miR-4435 derived from CAFs could suppress CD8⁺ T cells effector function, contributing to immune resistance, while knockdown of miR-4435 in CAFs-exo could foster CD8⁺ T cells effector function and enhanced the sensitivity of anti-PD-1 therapy in GC. Collectively, exosomal miR-4435 derived from CAFs suppress ferroptosis and CD8⁺ T cell effector function in GC via mediating NDUFA10. Our results highlight exos-transfered miR-4435 as a potential therapeutic target in GC.

Diffuse-type tenosynovial giant cell tumor (D-TGCT) is an uncommon synovial neoplasm. Hip involvement is rare and may be difficult to recognize because symptoms are nonspecific and osseous erosion can mimic more aggressive infectious, inflammatory, or neoplastic processes. We report a case of hip D-TGCT that presented as an erosive acetabular lesion and required histopathologic and immunohistochemical confirmation.

A 56-year-old man presented with acute right hip pain and restricted motion after a recent febrile illness that had partially improved following empirical intravenous cefuroxime therapy. Magnetic resonance imaging (MRI) demonstrated diffuse intra-articular synovial proliferation with heterogeneous low-to-intermediate signal intensity on T1-weighted images, heterogeneous signal intensity on T2-weighted images, and heterogeneous enhancement after contrast administration. Computed tomography (CT) showed joint effusion and thinning and erosion of the anterior and inferomedial acetabular wall, whereas plain radiographs were unremarkable. Because the imaging and laboratory findings were inconclusive, the patient underwent surgical excision and synovectomy, curettage of the eroded acetabular wall, alcohol ablation, and autologous iliac bone grafting. Histopathologic examination demonstrated mononuclear cells, osteoclast-like multinucleated giant cells, foamy histiocytes, chronic inflammatory cells, and abundant hemosiderin deposition. Integration of the characteristic morphology, diffuse intra-articular growth pattern, imaging findings, and supportive immunohistochemistry established the diagnosis of D-TGCT. Microbiologic cultures were negative. No postoperative radiotherapy was administered. At the 6-month follow-up, the patient reported sustained pain relief and improved hip motion, although mild restriction of motion persisted.

Hip D-TGCT should be considered when an intra-articular hip lesion shows synovial proliferation with acetabular erosion, even when inflammatory findings raise concern for alternative diagnoses. Magnetic resonance imaging and computed tomography are complementary for defining soft-tissue extent and osseous involvement, but definitive diagnosis depends on clinicopathologic correlation. This case highlights the diagnostic value of histopathology and immunohistochemistry in destructive-appearing hip lesions.

Mucosal melanoma is a rare and aggressive malignancy arising from anatomically distinct mucosal sites that share a common melanocytic origin but differ in their clinical presentation, biology, and management. Accumulating evidence indicates that the anatomic site of origin fundamentally shapes clinical presentation, immune and microbial microenvironments, molecular drivers, and therapeutic vulnerabilities. In this review, we integrate epidemiologic, clinical, genomic, immunologic, microbiome, and translational data to systematically compare mucosal melanomas arising from the sinonasal tract, oral cavity, anorectal region, and vulvovaginal tract. We highlight striking site-specific differences in patterns of presentation and metastasis, immune and microbiome composition, enrichment of actionable molecular alterations, and responses to therapies. We further discuss how current preclinical models often fail to account for this biologic diversity, limiting translational progress. Collectively, these data support viewing mucosal melanoma as a unified disease entity with clinically meaningful heterogeneity shaped by anatomic site of origin, with important implications for classification, clinical management, and trial design.

This study investigated how inflammatory cell death-associated regulators influence the prognosis of lung adenocarcinoma (LUAD) and elucidated their underlying mechanisms.

LUAD RNA-seq data from UCSC-Xena (training) and GSE72094 (validation) were analyzed. Inflammatory cell death regulators were identified, and LUAD subtypes were classified based on their expression. Subtypes were compared with respect to prognosis, clinical features, immune microenvironment, HLA genes, and immune checkpoints. Prognosis-related regulators and independent factors were identified, and a RiskScore model was built. Genomic alterations, drug sensitivity, immunotherapy response, and metabolic differences were analyzed across risk-stratified cohorts. Knockdown of TFDP1 in A549 cells was performed in vitro, and its effects on cell function were evaluated via RT-qPCR, Western blot, CCK-8, Transwell, and flow cytometry.

The research revealed 15 upregulated and 9 downregulated genes associated with inflammatory cell death, which were employed to stratify LUAD cases into two subtypes (Cluster 2 exhibited longer overall survival and higher immune/stromal scores). The seven-gene prognostic model (comprising BAK1, BMF, CYCS, FADD, IL1A, TFDP1, and YWHAG) demonstrated robust predictive power for LUAD patient survival risk. Notably, the high-risk cohort exhibited higher TIDE scores and lower IPS scores than the low-risk group. IL1A was positively correlated with 11 immune cell types and negatively correlated with 4. Drugs such as docetaxel and parthenolide may target this model. The study identified significant differences in 14 metabolic pathway enrichments between risk groups, particularly in fatty acid and fructose metabolism. Experimental validation confirmed TFDP1 upregulation in LUAD, and its knockdown suppressed A549 cell proliferation, migration, and invasion while inducing apoptosis.

A seven-gene inflammatory cell death-based signature for LUAD was developed, highlighting its role in immune regulation and its potential for immunotherapy. Experimental validation identified TFDP1 as a key regulator of inflammatory cell death processes in LUAD progression.