This meta-analysis assessed the clinicopathological significance of GLI1 in hepatocellular carcinoma (HCC). We systematically searched PubMed, Web of Science, Embase, Cochrane Library, Wan Fang, and CNKI for studies through October 2025. Studies assessing GLI1 by immunohistochemistry in HCC tissue and reporting its clinicopathological correlations were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Publication bias and sensitivity analyses were performed, and subgroup analyses were conducted when > 4 studies were available. Analysis of ten studies (n = 974) showed significant GLI1 upregulation in HCC versus non-tumorous tissues (OR = 7.06, 95% CI 3.21-15.54, P < 0.0001). Elevated GLI1 was associated with intrahepatic metastasis (OR = 2.51, 95% CI 1.42-4.43, P = 0.002), vascular invasion (OR = 2.98, 95% CI 1.64-5.42, P < 0.001), hepatitis B virus (HBV) infection (OR = 2.32, 95% CI 1.28-4.20, P = 0.006). The significance of advanced pTNM stage (OR = 3.03, 95% CI 1.29-7.10, P = 0.011) disappeared after adjusting for publication bias (adjusted OR = 1.94, 95% CI 0.85-4.40). No significant associations were found with patient age, liver cirrhosis, serum AFP level, and tumor size. Findings are based on observational studies with heterogeneity in GLI1 assessment; evidence certainty for several outcomes is low or very low. These findings support the hypothesis that GLI1 might be involved in aggressive HCC phenotypes and warrant its investigation in future, standardized prospective studies to assess its potential clinical utility.Trial registration: The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42024500731).

Circulating tumor DNA (ctDNA) is a minimally invasive biomarker that enables molecular profiling and prognostic stratification in cancer. This meta-analysis evaluated the prognostic significance of ctDNA in metastatic prostate cancer (mPC). PubMed, Web of Science and Scopus were searched from inception to September 15, 2025 for studies assessing ctDNA and survival in prostate cancer. Hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were extracted; when unavailable, HRs were reconstructed from published survival curves. Meta-analyses were performed according to ctDNA detectability, ctDNA levels and ctDNA-detected gene mutations. About 13 studies including 18,575 patients were eligible. Across 9 studies, detectable ctDNA was associated with significantly worse PFS (HR = 1.65, 95% CI: 1.22-2.22) and OS (HR = 2.20, 95% CI: 1.92-2.51) versus undetectable ctDNA. In patients receiving androgen receptor pathway inhibitors and in mCRPC, ctDNA negativity consistently correlated with longer PFS and OS. Gene-level analyses showed that AR, CDK6/12, MYC, PIK3CA, and BRCA1/2 mutations in ctDNA were linked to inferior PFS, whereas BRCA1/2 mutations did not significantly worsen OS. About 5 studies examined ctDNA levels: higher ctDNA levels predicted poorer survival (PFS: HR = 1.68, 95% CI: 1.18-2.38; OS: HR = 2.43, 95% CI: 1.50-3.93), and lower levels were associated with better outcomes in ARPI-treated and mCRPC patients. In mPC, ctDNA detectability and elevated ctDNA levels are strongly associated with adverse survival. Quantitative ctDNA profiling, including assessment of key gene mutations, offers a clinically relevant tool to refine risk stratification and to support molecularly informed treatment selection and monitoring where clinically validated.

BACKGROUND: Ropeginterferon alfa-2b is increasingly used as a long-acting interferon therapy for polycythemia vera (PV), providing hematologic and molecular benefits. However, clinical studies have implemented different dose-escalation strategies, and their impact on outcomes has not been systematically evaluated. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library (September 24, 2025) identified studies reporting clinical outcomes of ropeginterferon in PV. Nine studies met eligibility criteria. Two reviewers independently extracted data, and meta-analyses were conducted using random-effects models. Subgroup analyses compared slow dose-up (SDU) and rapid dose-up (RDU) regimens at 1-, 2-, and 3-year follow-up when available. RESULTS: The pooled 1-year complete hematologic response (CHR) rate was 0.59 (95% CI, 0.47–0.71). RDU regimens yielded significantly higher CHR than SDU at both 1 year (0.67 vs. 0.41; p < 0.001) and 2 years (0.75 vs. 0.63; p = 0.038). Molecular response (MR) also favored RDU at 1 year (0.59 vs. 0.36; p < 0.001), with differences diminishing at 2 years. The pooled 1-year reduction in JAK2 V617F allele burden was − 22.2% (95% CI, − 34.2% to − 10.2%; p < 0.001). Safety outcomes were favorable, with low rates of thrombosis (4%), serious adverse events (5%), and treatment discontinuation (7%). CONCLUSIONS: Ropeginterferon alfa-2b provides meaningful hematologic and molecular responses with an acceptable safety profile in PV. Rapid dose-escalation facilitates earlier CHR and MR without increasing toxicity, suggesting titration speed as an important determinant of early treatment optimization.

This systematic review aims to comprehensively evaluate the clinicopathological and molecular features of superficial CD34-positive fibroblastic tumour (SCD34FT), a recently described intermediate-grade soft-tissue neoplasm recognised in the 5th edition of the WHO classification of soft tissue tumours.

Salivary gland tumors (SGTs) are rare and biologically heterogeneous neoplasms for which conventional histopathological and single-platform molecular analyses have provided limited insights into disease mechanisms and therapeutic vulnerabilities. Advances in high-throughput technologies now enable integration of different molecular layers, offering unprecedented resolution of tumor complexities. We conducted a systematic review of studies published between 2001 and 2026 that applied multi-omics integration to human SGTs, requiring the combination of at least two omics layers. Seventy-eight studies met the inclusion criteria, most of which were observational (65.4%) and conducted in high-income countries (98.7%). Research were predominantly focused on malignant tumors (85.9%), particularly adenoid cystic carcinoma (38.5%), and frequently relied on formalin-fixed paraffin-embedded samples (55.7%). Genomic and transcriptomic integration was the most commonly used strategy (74.4%), typically supported by immunohistochemistry (61.5%) and in situ hybridization (38.5%) for biological validation. Overall, multi-omics studies have advanced molecular classification in selected tumor types, enabled the generation and validation of biologically faithful in vitro and in vivo models, identified prognostically relevant subgroups, and revealed actionable molecular vulnerabilities. However, despite these advances, clinical translation remains limited. Future progress will depend on prospective, clinically integrated, and functionally validated multi-omics studies to enable meaningful implementation of precision medicine for SGTs.

This study reports a rare case of mixed ovarian carcinoma composed of squamous cell carcinoma (SCC) and high-grade serous carcinoma (HGSC) arising from endometriosis, and provides a systematic review of the relevant literature.

Glioblastoma (GB), defined as IDH-wildtype CNS WHO grade 4 tumour according to the 2021 WHO classification of CNS tumours, remains a uniformly lethal malignancy in which the efficacy of temozolomide (TMZ) continues to be constrained by both intrinsic tumur biology and the pharmacological barrier imposed by the blood-brain barrier (BBB). Given the central role of the ABCB1 (MDR1/P-glycoprotein) efflux transporter in regulating CNS drug disposition, germline variation in ABCB1 has been proposed as a potential determinant of interindividual variability in TMZ response. This systematic review synthesised clinical evidence from four independent studies, encompassing more than 400 GB patients, evaluating the association between ABCB1 polymorphisms and TMZ efficacy and patients' survival. Across the available literature, the influence of ABCB1 genetic variation emerged as limited and inconsistent. An early study reported a marked survival advantage for carriers of the ABCB1 C1236T C/C genotype treated with TMZ, suggesting reduced efflux and enhanced drug exposure. However, subsequent investigations, including epigenetic analyses, high-quality multivariate survival modelling and a pharmacokinetic study demonstrating genotype-dependent differences in plasma TMZ concentrations, did not replicate a corresponding survival effect. Across the remaining cohorts, common variants such as 1236C>T, 2677G>T/A, 3435C>T and 1199G>A showed no robust association with clinical outcome, indicating that transporter-mediated modulation is likely overshadowed by dominant prognostic drivers, including MGMT methylation, IDH status and tumour heterogeneity. Collectively, current evidence does not support ABCB1 polymorphisms as reliable predictive biomarkers of TMZ response in GB. Nonetheless, the pharmacokinetic signals observed, together with emerging technologies capable of selectively modulating efflux activity at the tumour-BBB interface, point to a continued role for ABCB1 in future therapeutic strategies. Integration of transporter genomics with spatial pharmacokinetics and molecular stratification will be essential to refine drug delivery and improve outcomes in GB.

Focused ultrasound (FUS) is a noninvasive modality for targeted delivery of therapeutic agents across the blood-brain barrier (BBB). We conducted a systematic review and meta-analysis to evaluate the efficacy of FUS-mediated gene therapy in preclinical orthotopic glioblastoma (GBM) in vivo models.

Uterine fibroids are the most common benign gynecological tumors, affecting up to 70-80% of women, yet still lack clinically validated biomarkers for disease stratification, monitoring, or therapeutic targeting. Advances in multi-omics technologies offer unprecedented opportunities for biomarker discovery; however, their application in fibroid research remains fragmented across platforms, biological samples, and study designs, limiting translational progress.

BACKGROUND: Spatial and temporal intratumoral heterogeneity (ITH) remains a major challenge in the diagnosis, prognosis, and treatment of breast cancer. Recent advances in single-cell and spatial omics technologies have enabled unprecedented resolution of subclonal architectures, evolutionary trajectories, and microenvironmental interactions. This systematic and conceptual review aimed to synthesize and integrate current evidence on spatiotemporal ITH in human breast cancer, bridging empirical data with mechanistic interpretation through high-resolution profiling platforms. METHODS: We conducted a systematic review following PRISMA 2020 guidelines, searching three databases (PubMed, Scopus, and Web of Science) and screening 1037 records published between January 2018 and May 2025. 19 original studies were included based on predefined eligibility criteria targeting single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, or multi-omics approaches applied to human breast tumor samples. Data extraction focused on study design, technologies used, subclonal dynamics, spatial/temporal resolution, tumor–immune interactions, and risk of bias. RESULTS: The included studies analyzed over 400,000 single cells from diverse breast cancer subtypes, with a predominance of triple-negative breast cancer. Subclonal plasticity was a recurrent feature, often characterized by EMT (epithelial-to-mesenchymal transition) signatures, cell-cycle heterogeneity, and immune evasion. Spatial analyses revealed discrete ecological niches shaped by immune exclusion and stromal patterning, while temporal assessments uncovered therapy-driven clonal selection, metabolic reprogramming, and enhancer remodeling. Interclonal and tumor–immune communication were consistently associated with poor prognosis or therapeutic resistance. Most studies were judged to have low or moderate risk of bias, with transparent reporting and accessible data pipelines. CONCLUSIONS: Single-cell and spatial omics studies provide critical insights into the evolutionary ecology of breast cancer. By conceptually integrating spatial, temporal, and microenvironmental dimensions, this review highlights convergent evolutionary programs underlying tumor aggressiveness and resistance. Spatiotemporal ITH is a key driver of disease progression, and its systematic characterization could inform biomarker development, personalized therapies, and future multi-modal diagnostics. Continued integration of spatial, temporal, and functional data is essential to move from descriptive maps to clinically actionable frameworks.

Lung cancer is the second most common malignancy and the leading cause of cancer-related mortality worldwide. While tobacco exposure remains the main risk factor, 15-20% of cases occur in never-smokers, suggesting a role for genetic predisposition. Although infrequent compared to somatic alterations, germline alterations may contribute to non-small cell lung cancer (NSCLC) susceptibility, with implications for risk assessment, targeted therapy, and family counselling.

Invasive lobular breast carcinoma (ILC) differs from invasive ductal breast carcinoma (IDC) with respect to genetic alterations and risk factors. We aimed to quantify differences in the prevalence of germline BRCA1/2 mutations between these two patients' populations.

The latest generation of liquid biopsies incorporates multi-omic features, including genomics, methylomics, and fragmentomics. Machine learning (ML) approaches have been proposed to synthesize these complex biological data for the development of diagnostic classifiers. This study aims to evaluate the integration of ML with circulating cell-free DNA (cfDNA) analysis for early cancer detection.

BackgroundSERPINE1 has attracted considerable attention in tumor biology, but its clinical importance in head and neck squamous cell carcinoma (HNSCC) is not yet clear. We therefore examined whether SERPINE1 expression is related to survival in patients with HNSCC.MethodsWe searched three major databases (PubMed, EMBASE, and the Cochrane Library) and identified observational studies reporting survival outcomes in relation to SERPINE1 expression through November 11, 2024. From eligible reports we extracted data on progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS), and calculated pooled hazard ratios (HRs) using random-effects models.ResultsEleven studies including 733 individuals with HNSCC met the inclusion criteria. Across these cohorts, higher SERPINE1 expression was consistently linked with shorter OS (HR 2.81, P = 0.003) and shorter DFS (HR 1.57, P = 0.004). In contrast, no clear associations were observed for PFS or DSS (P ≥ 0.05).ConclusionCurrent evidence suggests that increased SERPINE1 expression is associated with an unfavorable prognosis in HNSCC, particularly for OS and DFS. Larger prospective studies are needed to confirm these findings and to determine how SERPINE1 assessment might be incorporated into risk stratification and treatment planning for patients with HNSCC.

An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer (SCLC). The systematic review aimed to summarize the characteristics of ferroptosis from its pathogenetic role to translational therapeutic implications in SCLC.

<p>Introduction: Circulating tumor DNA (ctDNA) assays are emerging as promising noninvasive tools for colorectal cancer (CRC) screening. This updated systematic review and meta-analysis evaluated the diagnostic accuracy of blood-based ctDNA assays for early CRC detection in asymptomatic adults.

Up to 1.6% of patients with endometriosis develop epithelial ovarian carcinoma. The genetic overlap between endometriosis and ovarian cancer has not been fully characterized. This review aims to describe the current literature on mutations correlated with endometriosis-associated epithelial ovarian carcinoma.

Background and Objectives: Melanoma is an aggressive cutaneous malignancy with a high recurrence rate even after complete resection. Circulating tumour DNA (ctDNA) has emerged as a promising biomarker for detecting minimal residual disease (MRD), assessing tumour burden, and predicting recurrence. This study aims to evaluate the clinical utility of ctDNA analysis in determining completeness of melanoma resection and disease staging. Materials and Methods: A systematic review was conducted in accordance with PRISMA guidelines, searching PubMed and Web of Science for studies published between January 2017 and February 2025. Eligible studies assessed ctDNA before, during, or after melanoma resection to evaluate surgical completeness and staging. Studies without perioperative ctDNA assessment or which focused solely on immunotherapy efficacy were excluded. Results: Fourteen studies with 1077 patients met the inclusion criteria. Preoperative ctDNA detection correlated with advanced stage, greater tumour burden, and poorer survival. Postoperative ctDNA persistence was strongly associated with recurrence, often detectable months before clinical relapse. In most patients remaining disease-free, ctDNA cleared within weeks after surgery. ctDNA levels reflected metastatic spread, though sensitivity was lower for brain lesions. Across studies, undetectable postoperative ctDNA was consistently linked to longer recurrence-free survival. Conclusions: Perioperative ctDNA analysis shows promise as a prognostic biomarker for detecting residual disease and anticipating relapse in melanoma. However, heterogeneity in patient cohorts, study design, and ctDNA detection methods limits immediate clinical application. Large, standardized prospective trials are needed to validate ctDNA for perioperative management.

Epithelial Ovarian Cancer (EOC) is the most lethal gynecological malignancy, with a high rate of recurrence due to minimal residual disease (MRD). Traditional surveillance methods have limited sensitivity for detecting MRD. ctDNA has emerged as a promising biomarker for real-time tumor monitoring and early detection of MRD.

Detection of extranodal extension (ENE) can guide treatment planning for patients with oropharyngeal squamous cell carcinoma (OPSCC). This systematic review identifies molecular biomarkers predictive of ENE in both Human Papillomavirus (HPV)-positive and HPV-negative OPSCC.