Background/Objective: Although most melanocytic lesions are diagnosed as benign or malignant by histopathologic evaluation, with or without the aid of immunohistochemistry, diagnosis may remain uncertain in a minority of cases. Assessment of copy number abnormalities (CNAs) may provide sufficient additional evidence to favor either a benign or malignant diagnosis in both pediatric and adult cases and in melanocytic lesions of various subtypes, including Spitzoid, mucosal, and acral. CNAs are common in melanomas, while they are rare, with few exceptions, in benign lesions. Detection of CNAs by fluorescence in situ hybridization (FISH) and chromosomal microarray (CMA) has been well established for melanocytic lesions, with advantages and disadvantages for each. The objective of this meta-analysis was to evaluate the utility of CNA testing for the diagnosis of melanoma, across subtypes, when a lesion remains ambiguous after histopathologic and immunohistochemical assessment. In addition, the utility of CNAs to determine prognosis in established diagnoses of melanoma was also evaluated. Methods: The Cancer Genomics Consortium Working Group for Melanocytic Lesions reviewed published data from January 1998 through September 2022 of CNAs in melanocytic lesions detected by either FISH or CMA and conducted a meta-analysis of the findings. Results: Specific abnormalities common in primary cutaneous melanomas of various subtypes and uveal melanomas were enumerated. Differences in CNAs found in primary versus metastatic lesions were also determined, and published evidence for prognosis was summarized. Conclusions: The working group established evidence-based recommendations for the use of CNA testing for evaluation of ambiguous melanocytic lesions.

Metastatic castration-resistant prostate cancer (mCRPC) remains a clinically aggressive and lethal disease. Circulating tumor DNA (ctDNA), as a minimally invasive biomarker, has shown prognostic utility in several solid tumors. However, its clinical relevance in mCRPC has not been comprehensively elucidated.

Microsatellite instability (MSI), programmed death-ligand 1 (PD-L1) expression, and Epstein-Barr virus (EBV) positivity are emerging biomarkers in gastric cancer prognosis and treatment selection, particularly in immunotherapy. This review evaluates their prognostic significance through a systematic review and meta-analysis.

In proficient mismatch repair (pMMR) non metastatic rectal cancer, standard neoadjuvant chemoradiotherapy (nCRT) yields low pathological and clinical complete response rates. Early randomized trials suggest adding PD 1 inhibitors may increase response but randomized evidence has not been synthesized.

Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies, with nearly 80% of patients diagnosed at advanced stages due to the absence of early symptoms and the nonspecific nature of later clinical manifestations. This highlights the urgent need for robust molecular biomarkers that can refine patient stratification and guide personalized therapeutic approaches. A major determinant of OC aggressiveness is the epithelial-to-mesenchymal transition (EMT), a transcriptionally driven program that represses epithelial identity while promoting mesenchymal traits, thereby enhancing invasion, dissemination, recurrence, and resistance to therapy. EMT dysregulation is widespread in OC and fuels tumor heterogeneity, metastatic spread, and chemoresistance. To investigate the contribution of EMT-related genes in OC biology, we analyzed whole-genome sequencing and RNA-seq data from 419 patients in The Cancer Genome Atlas (TCGA) Pan-Cancer Atlas, assessing their genomic and transcriptomic alterations. We integrated these findings with transcriptomic and drug-sensitivity data from the CTRPv2 portal, performing Pearson correlation analyses to identify therapeutic vulnerabilities associated with EMT gene expression. Our analysis identifies recurrent genomic and transcriptomic alterations across several EMT-associated genes. Notably, we identified a four-EMT gene signature (EFNA1, OVOL2, GATA3, and DSG2) whose expression correlates with differential sensitivity to VEGFR and EGFR inhibitors in OC cell lines. Overall, these results suggest that EMT-driven molecular changes contribute to the onset and progression of OC and highlight a subset of EMT genes as promising predictive biomarkers for targeted therapy responses.

Neuroblastoma (NB) is the most prevalent extracranial solid tumor in children. Therefore, urgent exploration of novel therapeutic targets and more effective approaches is imperative to enhance the prognosis of these children.

Gliomas are intracranial tumors characterized by limited diagnostics and treatment approaches. Blood-circulating miRNAs represent a regulatory class of molecules that change their expression under pathological conditions and can relatively easily be detected. The present study evaluates the diagnostic potential of blood-circulating miRNAs in glioma. All grades of gliomas are included in the analysis. The articles were retrieved from the PubMed, Web of Science and Scopus databases up to October 2025. The studies were considered to be eligible if they used glioma patients and healthy controls and compared their miRNA levels, indicating sensitivity and specificity values. Risk of bias was assessed using the QUADAS-2 tool. The collected data was pooled by the STATA 19.0 MP bivariate random effects model and indicated heterogeneity using the I2 statistic value. To identify possible reasons for heterogeneity, we utilized subgroup analysis and meta-regression. Publication bias was assessed with Deeks' funnel plot, and the test diagnostic potential was evaluated with Fagan's nomogram. We analyzed 31 original reports covering 2299 glioma patients and 1719 healthy controls. A meta-analysis on 59 data points extracted from the analyzed papers was conducted. The combined pooled sensitivity was found to be equal to 0.83 (95%CI: 0.80-0.86), the specificity 0.88 (95%CI: 0.85-0.90), the positive likelihood ratio 6.7 (95%CI: 5.4-8.5), the negative likelihood ratio 0.19 (95%CI: 0.16-0.23), and the diagnostic odds ratio 35 (95%CI: 25-50). An SROC analysis revealed an AUC equal to 0.92 (95%CI: 0.90-0.94). The reported diagnostic parameters imply that blood-circulating miRNAs hold the potential to be developed into diagnostic biomarkers for glioma identification. However, the high heterogeneity in the analyzed studies suggests that the results should be considered as exploratory only.

The high prevalence (>5%) of autoimmune hypothyroidism (AIHT) provides a unique opportunity to dissect genetic contributions to systemic and organ-specific autoimmunity. Here we performed a genome-wide association meta-analysis of 81,718 AIHT cases in FinnGen and the UK Biobank, identifying 418 independent signals (P < 5 × 10-8). At 48 of these loci, a protein-coding variant is, or is highly correlated (r2 > 0.95) with, the lead variant, including Finnish-enriched coding variants in LAG3, ZAP70 and TG. We demonstrated that ZAP70:T155M reduces T cell activation and broadly compare large-scale scans of nonthyroid autoimmunity and thyroid-stimulating hormone levels with a Bayesian classifier to assign loci into distinct groupings, estimating that 38% are involved in general autoimmunity whereas 20% are thyroid specific. We further identified substantial antagonistic pleiotropy, with 10% of AIHT loci showing a consistent protective effect against skin cancer. The AIHT results, including numerous genes encoding checkpoint proteins, support the causal role of natural immune variation influencing cancer outcomes.

Mismatch repair deficiency (dMMR) and microsatellite instability (MSI-H) cancers exhibit high immunogenicity and are highly responsive to immune checkpoint inhibitors. In patients with locally advanced dMMR/MSI-H colorectal cancer (CRC), neoadjuvant immunotherapy (NIT) has demonstrated unprecedented pathological complete response (pCR) rates, suggesting nonoperative management strategies may be possible. There remains a discrepancy between radiological assessment and pathological responses to NIT in CRC.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is characterized by extensive immune infiltration, yet immune evasion remains a hallmark. In this study, we aimed to leverage publicly available datasets to identify EBV-host gene interactions and re-map their expression at single-cell resolution. We conducted a meta-analysis to identify differentially expressed genes, mapped these genes to EBV-host interaction data, constructed a network, and performed pathway enrichment. Single-cell RNA sequencing datasets were used to map these genes at cellular resolution. We analysed differences in cell cycle, immune signaling, cell-cell interactions, and assessed prognostic associations of UPS signature using the GEPIA2 platform. We identified 85 EBV-interacting DEGs regulated by lytic-phase proteins. Clustering highlighted genes related to the ubiquitin-proteasome system (UPS). Single-cell analyses confirmed elevated UPS-related gene expression in NPC. UPS-High cells exhibited lower proliferative activity, enriched stemness signaling, and reduced antigen presentation and immune activation, whereas UPS-Low cells showed marked upregulation of growth-promoting pathways. High UPS expression was associated with poorer outcomes in pan-cancer, head and neck squamous cell carcinoma, and marginally significant in the small NPC datasets. The proportion of UPS-High cells varied widely across patients. UPS activity, influenced by EBV lytic proteins, is linked to immune evasion, stemness, proliferation, and adverse prognosis. These findings support UPS as a potential biomarker and therapeutic target in NPC, warranting validation and functional studies.

The long non-coding RNA HOTAIR has been implicated in tumor initiation and progression, and multiple case-control studies have explored whether common HOTAIR single-nucleotide polymorphisms influence susceptibility to gastrointestinal (digestive system) malignancies. However, published findings remain inconsistent across populations and cancer types.

Antibody-related immune phenotypes reflect long-term host-pathogen interactions and immunogenetic regulation, and have been increasingly implicated in cancer susceptibility. In ovarian cancer, observational associations between immune responses and disease risk remain difficult to interpret due to confounding and potential reverse causation. Genetic analyses may help clarify whether specific antibody immune response profiles are linked to ovarian cancer risk. We investigated the associations between 46 genetically predicted antibody immune response phenotypes and ovarian cancer using a 2-sample Mendelian randomization framework. Genetic instruments for antibody traits were obtained from large genome-wide association studies, while ovarian cancer summary statistics were derived independently from the FinnGen R12 and OpenGWAS resources. Causal estimates were derived primarily using inverse-variance weighted models and subsequently synthesized across datasets to improve precision. Multiple testing adjustment was applied, and additional analyses were conducted to assess robustness and causal directionality. Across the evaluated antibody phenotypes, most showed no evidence of a causal association with ovarian cancer risk. After meta-analysis and correction for multiple comparisons, genetically predicted anti-polyomavirus 2 immunoglobulin G (IgG) seropositivity was associated with a modest increase in ovarian cancer risk (odds ratio = 1.062, 95% confidence interval: 1.027-1.099). Sensitivity analyses did not indicate substantial pleiotropic bias, and reverse-direction analyses provided no support for ovarian cancer influencing anti-polyomavirus 2 IgG levels. These findings suggest that genetic liability to anti-polyomavirus 2 IgG seropositivity, as a marker of immune response rather than active infection, is modestly associated with ovarian cancer risk in individuals of European ancestry. Although the effect size is small, the results highlight a potential role for antibody-mediated immune processes in ovarian cancer etiology and warrant further investigation in diverse populations and experimental settings.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Approximately 30% of patients present alterations in the FMS-like receptor tyrosine kinase 3 (FLT3) gene, which are associated with poor prognosis. FLT3 inhibitors - midostaurin (first-generation), gilteritinib and quizartinib (second-generation) - have been developed to block FLT3 activation. Given the need of optimizing treatment in FLT3-mutated AML, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the safety profiles of FLT3 inhibitors. Following the PRISMA statement, we searched Embase, MEDLINE and Cochrane Library. The Cochrane Risk of Bias Tool for RCTs was used for quality assessment. Of 2132 references, seven RCTs, involving 2409 adult patients, met inclusion criteria: quizartinib and midostaurin in two trials each and gilteritinib in three. The most frequently reported adverse events (AEs) were classified under the System Organ Class (SOC) Blood and lymphatic system disorders (N = 5474, 58.4% of them related to FLT3 inhibitors). The most frequently observed non-hematological AEs were gastrointestinal disorders, pyrexia, elevated ALT/AST and headache. FLT3 inhibitors are not associated with a significant increase in the risk of AEs compared to standard treatments. No meaningful differences in AE risk were observed among the three drugs. The only exception was an higher risk of ALT increased with gilteritinib (RR = 2.40, 95% CI: 1.16-4.95). Future studies should stratify safety outcomes by demographic and clinical characteristics and incorporate long-term follow-up for a more comprehensive safety assessment in clinical practice.

IntroductionMachine learning (ML)-based analysis of cell-free DNA (cfDNA) has emerged as a promising strategy for multi-cancer early detection (MCED). However, reported diagnostic performance varies widely across studies, and many estimates are derived from training or enriched cohorts, limiting their relevance to independent validation and real-world settings.MethodsWe conducted a systematic review and diagnostic accuracy meta-analysis of ML-based cfDNA assays for MCED. Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched from inception to February 2, 2025. Only independent validation or testing datasets were included; all training datasets were excluded. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves were estimated using a bivariate random-effects model. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity.ResultsThirteen studies comprising 23 independent datasets and 14,892 participants were included. The pooled sensitivity was 0.78 (95% CI: 0.66-0.87), and the pooled specificity was 0.96 (95% CI: 0.90-0.98). The summary area under the curve (AUC) was 0.94, with a DOR of 76.6. Substantial between-study heterogeneity was observed (I2 > 90%), with geographic region, sample size, and cfDNA biomarker type identified as major contributing factors.ConclusionML-based cfDNA assays demonstrate consistently high specificity and moderate-to-high sensitivity across independent validation datasets, supporting their potential role in multi-cancer early detection. However, diagnostic performance is highly context dependent and strongly influenced by study design, population characteristics, and analytical choices. These findings highlight the need for large-scale, prospective, population-based validation before widespread clinical implementation.

Colorectal cancer is thought to develop through the stepwise accumulation of somatic mutations. Recent years have seen the publications of several studies greatly advancing our understanding of the molecular events driving the disease. However, individual studies tend to be small and additional insights may be obtained through the combination of data from multiple sources. We performed targeted sequencing of 2172 colorectal cancers from Icelandic patients and combined these data with publicly available mutation calls from 9 515 additional tumours collected from the literature. Analysing microsatellite stable (MSS) and instable (MSI) tumours separately, we find evidence of positive selection of mutations in 112 genes that replicate across multiple studies of patients with diverse demographics. We carried out a meta-analysis of conditional selection, identifying 57 gene pairs where a mutation in one gene influences the selection of the other. We describe many associations with tumour phenotypes, including a strong association between mucinous histology and mutations in the transcription growth factor beta (TGFb) pathway, only in MSS tumours. Our study demonstrates how combining evidence from multiple sources allows for new discoveries in cancer genomics.

Cervical cancer (CC) is one of the most prevalent cancers worldwide. Single nucleotide polymorphisms (SNPs) of the epidermal growth factor receptor (EGFR) and epidermal growth factor (EGF) genes are associated with cancers in diverse populations; However, the roles of these genes in CC are uncertain. Associations between these SNPs and CC risk, as well as the risk of pathological type and clinical stage, were analysed. On thebasis of our data, a cross-cancer meta-analysis was performed to assess the roles of nine SNPs of the EGFR and EGF genes in cancer susceptibility. Finally, SNP‒SNP interactions were analysed in the present study. Our data showed that the potential SNP‒SNP interaction between EGFR and EGF may be associated with CC development in Chinese Han individuals. The meta-analysis indicated that these SNPs in EGFR and EGF may be associated with cancer risk, particularly in Asians. Cross-cancer SNP‒SNP interaction analysis demonstrated that the 9-SNP model exhibited significant synergistic effects in predicting cancer risk.

Early studies indicate that neoadjuvant immune checkpoint inhibitors (ICIs) induce high rates of tumor regression in localized deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) gastric and gastroesophageal junction (GEJ) cancers, raising interest in nonoperative management (NOM). Most available data, however, come from small, nonrandomized cohorts. A systematic synthesis was undertaken to better characterize efficacy and safety outcomes.

Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in the DNA mismatch repair (MMR) genes MSH2, MSH6, MLH1 and PMS2. The objective of this systematic review was to estimate the prevalence of germline mutations in MMR genes among patients with upper tract urothelial carcinoma (UTUC).

Lung cancer exhibits highest incidence among all cancer types worldwide and even after rigorous research and advanced treatment strategies, it constitutes a primary cause of cancer-related mortality. Non-small cell lung cancer is the predominant subtype, constituting the majority of lung cancer cases. Therefore, exploring novel biomarkers is crucial for betterment of diagnostic and therapeutic approaches.

Micronuclei (MN) genotoxicity, linked to chromosomal anomalies, is a key biomarker for carcinogen exposure and cancer susceptibility, with higher frequencies observed in cancer patients. The micronuclei assay, using exfoliated buccal cells, offers a non-invasive method for diagnosing oral lesions caused by tobacco, betel nut, and alcohol. This review aims to systematically review micronuclei frequencies in buccal mucosal cells and assess their potential as genotoxicity markers in oral potentially malignant disorders (OPMD).