With the ever-increasing incidence of cutaneous melanoma (CM), early detection has become pivotal for ensuring patient survival. MicroRNAs (miRNAs) are promising diagnostic biomarkers owing to their stability and wide availability in various body fluids. This systematic review and meta-analysis evaluated the diagnostic performance of blood-based circulating free miRNAs and extracellular vesicle (EV)-derived miRNAs for CM. The study protocol was registered in PROSPERO (CRD420251125262). A total of 557 records were identified, with 11 studies included in the systematic review and 10 in the meta-analysis. Diagnostic performance was evaluated for all studies combined, and separately for individual miRNA and miRNA combinations. The bivariate model showed a pooled sensitivity of 0.86, specificity of 0.85, and diagnostic odds ratio (DOR) of 33.52. Separate analyses indicated that individual miRNAs yielded sensitivity, specificity, and DOR values of 0.80, 0.78, and 13.71, respectively. On the other hand, miRNA combinations achieved superior accuracy with a sensitivity of 0.91, specificity of 0.89, and DOR of 84.05. Subgroup analysis demonstrated that the plasma samples outperformed the other sample sources. Overall, circulating miRNAs exhibit strong potential as noninvasive diagnostic biomarkers for CM.

Several genomic risk stratification tests are available to predict the risk of metastasis and mortality for prostate cancer patients at the time of diagnosis. However, the evidence supporting the clinical utility of genomic risk stratification tools is fragmented, posing challenges in assessing their real-world clinical impact and cost-effectiveness.

The incidence and mortality of colorectal cancer (CRC) are steadily rising. Phosphatase-Tensin Homolog Deleted on Chromosome 10 (PTEN) expression is often dysregulated during tumourigenesis; however, its prognostic value in CRC remains debated. This study evaluated the correlation between PTEN expression and the clinicopathological characteristics of CRC patients, and its prognostic significance. A systematic literature review was conducted across Web of Science, PubMed, Cochrane Library, and CNKI up to June 2023. Thirteen studies with a total of 2,377 participants were included. PTEN expression was significantly lower in CRC tissues than in normal mucosa tissues. Positive PTEN expression was associated with better overall survival and favourable pathological features. No significant correlation was found with age, gender, differentiation grade, tumour size, or distant metastasis. Negative PTEN expression is a poor prognostic marker in CRC and may serve as a potential indicator for disease monitoring and outcome prediction. Key Words: PTEN, Colorectal cancer, Prognosis, Meta-analysis, Clinical characteristics.

Early-onset pancreatic adenocarcinoma (EOPA), defined as the diagnosis of pancreatic adenocarcinoma before the age of 50, is increasingly reported and may differ molecularly from average-onset pancreatic adenocarcinoma (AOPA). Understanding these differences is essential for precision medicine in this poor-prognosis malignancy.

Many studies using measured Body Mass Index (BMI) report an inverse association with lung cancer, but a few recent Mendelian randomization (MR) studies using genetically proxied BMI suggest a possible risk association. The aim of this study was to systematically evaluate and synthesize evidence on the association between lung cancer risk and both directly measured (i.e., clinically measured or self-reported) and genetically proxied BMI.

KRAS p.G12C (c.34G > T) inhibitors have been reported to have varying survival outcomes in CRC patients across studies. Hence, our review aimed to provide a comprehensive understanding of the efficacy and safety of these agents among the CRC population.

BACKGROUND: Breast cancer prognosis is the result of complex interactions between tumor biology, treatment, and host factors. While germline genetic variation is increasingly incorporated into breast cancer risk assessment and therapeutic decision-making, its role in determining prognosis remains incompletely defined. This systematic review and meta-analysis synthesizes available evidence on the association between germline genetic variants and breast cancer outcomes, with a focus on pathway-level effects. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, MEDLINE, Web of Science, and QInsight to identify studies published between January 2000 and June 2024. Published articles that evaluated associations between germline genetic variants and breast cancer prognosis were included. Eligible studies reported time-to-event outcomes, including disease-free survival (DFS), overall survival (OS), and other outcomes. Genes harboring prognostic variants were grouped into functional clusters using STRING. Primary analyses consisted of cluster-based multilevel random-effects meta-analyses, while global outcome-based meta-analyses were conducted as secondary, exploratory analyses. The protocol was registered in PROSPERO (CRD42022308746) and followed PRISMA guidelines. RESULTS: Fifty-four studies encompassing 253,768 women were included. Most participants were of European ancestry, with marked underrepresentation of Hispanic (0.21%) and Black (0.25%) populations. Cluster-based meta-analyses identified six biologically coherent pathways associated with adverse prognosis. The ERBB2–PI3K resistance network showed the strongest association with OS (HR = 3.47; 95% CI: 1.54–7.78) and DFS (HR = 1.70; 95% CI: 1.02–1.82). Immune-related cytokine pathways were consistently associated with poorer OS (HR = 2.29; 95% CI: 1.04–5.04) and DFS (HR = 1.49; 95% CI: 1.20–1.85). Germline variation in xenobiotic metabolism genes was significantly associated with OS (HR = 1.65; 95% CI: 1.24–2.20), while DNA repair genes were strongly associated with breast cancer–specific mortality (HR = 3.51; 95% CI: 1.80–6.85). Exploratory global meta-analyses pooling all variants demonstrated overall directional associations with OS (HR = 2.30) and DFS (HR = 1.49), with substantial heterogeneity. CONCLUSIONS: This systematic review and meta-analysis show that germline genetic variation influences breast cancer prognosis in a pathway-specific manner. These findings highlight the importance of biologically informed analytic strategies and underscore the need for large, ethnically diverse studies to validate pathway-level germline prognostic markers and support their integration into personalized breast cancer management.

MET exon 14 skipping mutations (METex14) or amplification drives a subset of non-small cell lung cancer (NSCLC). Tepotinib, a selective MET tyrosine kinase inhibitor (TKI), has shown promise in early trials; however, comparative efficacy and safety data across MET-altered subpopulations remain limited. This systematic review of six studies (546 patients) assessed the clinical outcomes of Tepotinib in METex14 or MET-amplified NSCLC. The primary endpoint was objective response rate (ORR); secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. The pooled objective response rate (ORR) was 52% (95% CI: 48–56%) and a disease control rate (DCR) of 76% (95% CI: 72–80%). Median PFS was 10.16 months, and median OS was 14.67 months. Subgroup analyses revealed no significant differences in ORR between METex14 (52%) and MET amplification (53%, p = 0.905) or between monotherapy (51%) and combination therapy (56%, p = 0.242). Common treatment-related adverse events (TRAEs) were grade 1–2 peripheral edema (50%) and diarrhea (36%); grade ≥ 3 TRAEs were infrequent (8% for edema). In conclusion, Tepotinib demonstrated comparable efficacy in METex14 and MET-amplified NSCLC with a manageable safety profile. The PFS benefit of combination therapy warrants further randomized trials. These findings support Tepotinib as a valuable therapeutic option for MET-altered NSCLC.

Melanoma, colorectal cancer (CRC), and hepatocellular cancer (HCC) overexpress the PD-1/PD-L1 pathway to evade the immune response. Immune Checkpoint Inhibitors (ICIs) suppress this mechanism but lack specificity, leading to immune-related adverse events (irAEs). Small-interfering RNA (siRNA) offers precise gene suppression but requires a protective delivery vector. Attenuated Salmonella, with tumor-targeting and immunomodulatory properties, is a promising carrier.

Glioblastoma (GBM) is an aggressive tumor with limited therapeutic options. Zika virus (ZIKV) has demonstrated activity against GBM; however, the cellular pathways behind this interaction remain unclear. We systematically reviewed open-access primary studies assessing differentially expressed genes (DEGs) in GBM models infected with wild-type or engineered ZIKV using transcriptomic approaches (inclusion criteria); reviews, restricted-access studies, commentaries, preprints, abstracts, and articles lacking data or not meeting these conditions were excluded (PROSPERO CRD420251077092). We performed a pathway analysis of reported DEGs. PubMed and Google Scholar were searched up to 5 March 2025; 139 records were identified and 5 met the eligibility criteria. Risk of bias was evaluated using an adapted ToxRTool for in vitro experiments and the SYRCLE RoB tool for in vivo models. Altogether, 4360 genes were reported as upregulated and 2072 as downregulated; 12 genes (DNAJB9, SESN2, PMAIP1, PPP1R15A, KLF4, ATF3, IFNB1, IFNL1, ANKRD33B, ZC3HAV1, OASL, and CCL5) were consistently upregulated, none were consistently downregulated. Pathway analysis of the studies providing complete DEG lists identified 23 commonly enriched pathways mostly related to interferon signaling. These findings may help guide future research in this field; nevertheless, methodological heterogeneity limits comparability, reinforcing the need for standardized protocols. Funding: ITpS, CNPq, and FAPEMIG.

Almost half of patients with triple-negative breast cancer (TNBC) develop brain metastasis (TNBCBM), a marker of poor prognosis. TNBC is a more aggressive breast cancer subtype which lacks ER, PR, and HER2 expression, and thus, exploring predictive biomarkers is crucial to improving TNBCBM outcomes through targeted therapy. To curate these biomarkers, peer-reviewed publications from 2010 to 2025 were extracted from PubMed, Scopus, Embase, Cochrane, and Web of Science if they evaluated clinicopathological biomarkers of TNBCBM. A total of 130 studies (60 clinical and 70 pre-clinical) were included. Publications most often featured transcriptomic studies, growth factor receptors, and immune microenvironment markers with 37, 19, and 17 studies identified, respectively. While TNBC aggressiveness has been linked to metastasis, advancing stage, and poor prognosis, several studies focused on utilizing circulating protein and transcriptomic biomarkers for early detection. While few pathways appeared specifically for TNBCBM, investigating these biomarkers further may allow for improved risk stratification, clinical trial design, patient selection, and therapeutic development. Identification of the most promising biomarkers will pave the way for improved prognosis of the most lethal complications of TNBC.

Triple-negative breast cancer (TNBC) is characterized by marked clinical and molecular heterogeneity, which underlies the limited success of currently available targeted therapies and results in most patients relying on cytotoxic chemotherapy. This therapeutic gap underscores the pressing need for novel therapeutic approaches, in which non-coding RNAs (ncRNAs) have emerged as promising candidates. In this systematic review, 35 pre-clinical studies published between 2020 and 2025 were analyzed to evaluate the therapeutic potential of targeting ncRNAs in TNBC, including miRNAs, lncRNAs, and circRNAs. The original articles employed in vivo tumor models to assess the therapeutic response of ncRNA expression modulation, using miRNA mimics, antagomiRs, ASOs, shRNAs, and siRNAs integrated into advanced targeted delivery systems, such as nanoparticles and exosomes. According to the selected studies, 28 specific ncRNAs were identified as actionable molecular targets. Modulation of these molecules consistently resulted in tumor growth suppression, metastasis inhibition, and restoration of sensitivity to standard chemotherapeutic agents. Collectively, the pre-clinical evidence presented in these studies positions ncRNA-based therapies as innovative, promising, and potentially effective strategies for advancing TNBC treatment.

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.

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.

BACKGROUND: Next-generation sequencing (NGS) technology has revolutionized oncology by detecting novel and rare somatic cancer mutations and identifying individuals with pathogenic germline variants, both of which can facilitate personalized medicine. By integrating NGS into routine diagnosis in Brazil, patients may benefit from improved treatment responses, however, several barriers to the implementation of NGS in Brazil exist. This review provides practical insights into how NGS can be integrated into diagnostics in public hospitals. METHODS: A comprehensive systematic review was conducted following the guidelines of the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA). PubMed, Medline, and Cochrane databases were queried for publications written in English, French, Portuguese, or Spanish from 2014 to February 2025. The research was conducted using Medical Subject Headings (MeSH), including terms such as NGS, public hospital, diagnostic, implementation and Brazilian Public Health System (SUS). RESULTS: Of the 7804 articles identified, 1233 were analyzed with only 10 meeting inclusion criteria. Current literature on NGS is largely centered in the Global North, with limited contributions from low- and middle-income countries. Key challenges included lack of access to molecular profiling and inadequate medical education (27% each), high costs of NGS (23%), data interpretation challenges (15%), and need for additional cost-benefit analyses (8%). Of note, only one paper conducted a cost-effectiveness analysis, demonstrating the utility of NGS in treating cancer. CONCLUSIONS: This systematic review highlights key gaps on NGS implementation in Brazil. There is a need for improved education for healthcare professionals and students to effectively incorporate NGS into clinical oncology practice, as well as strategies to lower costs of sequencing and systematic data interpretation pipelines. Despite these challenges, Brazil has the potential to lead NGS implementation in Latin America. Our experiences at a public hospital may be used as a model to implement NGS through meticulous procurement management, leveraging expertise from basic research, and integrating AI-driven data analysis platforms.

Genetic mutations and their phenotypic manifestation have been recognized as critical factors in tumorigenesis. However, the relationship between these mutations and the pathogenesis of uterine leiomyomas (UL) remains inadequately characterized. There is compelling evidence to suggest a genetic underpinning in UL development, alongside influences from epigenetics, environmental stimuli, growth hormones, and growth factors. A plethora of studies have tried to elucidate the genetic and epigenetic etiologies associated with UL, but the definitive implications of these findings remain unclear. An extensive systematic review was conducted to investigate the genetic etiologies of UL. This systematic review aimed to consolidate current knowledge on genetic and epigenetic causes of UL, offering a comprehensive perspective on the evidence and its relevance in other solid tumors. A secondary focus was to identify the most significant genetic association with the genesis of UL. A total of 60 articles were identified, and 10 chromosomes and 51 genes were found to be implicated in the development of UL. The main trend in fibroid research focuses on genetic abnormalities and aberrations as the etiology of UL development. It has been estimated that 40% of UL can be associated with chromosome-specific aberrations. Chromosomal gain, loss, rearrangement, single nucleotide polymorphism (SNP), and translocation are the most common aberrations associated with UL development. The most recurrent ones include chromosome X and 7q deletions, and rearrangements of 12q15, 6p21 and 10q22. MED12 has been identified as a gene of particular importance in the development of UL.

Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis. O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is a critical biomarker for guiding chemotherapy decisions, yet current testing requires invasive tissue sampling. This study aimed to systematically evaluate the diagnostic accuracy of artificial intelligence (AI) models using MRI for non-invasive prediction of MGMT promoter methylation status in GBM.

Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for monitoring minimal residual disease (MRD) and predicting recurrence in early-stage breast cancer (EBC). Despite growing interest, the prognostic impact of ctDNA detection in this setting remains to be fully elucidated.

Germline RET-p.C634Y heterozygous mutations are predominant in MEN2A, but homozygous cases and MEN2A-affected identical twins remain poorly characterized.

Prognostic biomarkers for advanced non-oncogene-addicted non-small cell lung cancer (NSCLC) remain limited. This PRISMA-compliant systematic review assessed the prognostic value of plasma circulating tumor DNA (ctDNA) at baseline and its dynamics during treatment. Cochrane, EMBASE, and MEDLINE were searched to February 27, 2025, identifying studies reporting hazard ratios (HRs) for overall survival (OS). Bias was evaluated using the Quality in Prognostic Studies tool, and publication bias with funnel plots and Egger's regression. Among 7118 records, 43 studies were included, spanning diverse designs, ctDNA assays, quantification units, and definitions of dynamic change. Detectable or elevated baseline ctDNA was associated with worse OS (HR 1.62; 95 % CI 1.40-1.87) with substantial heterogeneity and possible small-study bias. Increasing or persistent ctDNA during treatment was strongly prognostic for poor survival (HR 2.69; 95 % CI 2.35-3.09). Overall study quality was moderate to high. Plasma ctDNA shows consistent prognostic value, though clinical implementation is limited by methodological variability.