L1 cell adhesion molecule (L1CAM) has emerged as a potential prognostic biomarker in endometrial cancer. This systematic review and meta-analysis aimed to comprehensively evaluate the prevalence of L1CAM expression across molecular subtypes of endometrial cancer and its prognostic significance for survival outcomes.

Blood-based circulating tumour DNA (ctDNA) assays have emerged as a promising tool for minimally invasive colorectal cancer (CRC) screening. However, their diagnostic accuracy in asymptomatic, average-risk populations remains uncertain. This systematic review and meta-analysis aimed to synthesise current evidence on the performance of ctDNA-based blood tests for detecting advanced colorectal neoplasia (ACN), defined as the composite of invasive CRC and advanced precancerous lesions (APL).

Ovarian cancer is one of the deadliest gynecological malignancies, mainly because of its silent development and the lack of effective conventional methods for diagnosis. Because of their extraordinary stability in bio fluids and expression signatures that specifically correlate with tumors, circulating microRNAs (miRNAs) have received much attention as non-invasive diagnostic biomarkers. This meta-analysis evaluates the diagnostic value of circulating miRNAs for early ovarian cancer. A systematic literature review was performed in line with PRISMA-DTA guidelines in PubMed, EMBASE, and Web of Science until March 8, 2025. A total of 24 studies were eligible. Pooled diagnostic metrics (sensitivity and specificity, likelihood ratios, and diagnostic odds ratio (DOR)) were calculated based upon the bivariate random effect model. Summary receiver operating characteristic (sROC) curves were generated and subgroup and meta-regression analyses performed to investigate heterogeneity. Sensitivity analyses were performed to assess the strength of the pooled estimates. The combined sensitivity, specificity and DOR was 0.749 (95% CI: 0.702–0.791), 0.748 (95% CI:0.695–0.794) and 8.403 (95% CI: 6.308–11.194) respectively, which means a moderate-to-high diagnostic efficacy. Screening efficacy of serum-based and PBMC-based tests differed significantly at the DOR of 10.55 being maximum amongst serum assays. Biospecimen and regional differences contributed substantially to heterogeneity. The results were robust according to sensitivity analyses, and there was no obvious publication bias based on Deeks’ test (p = 0.08). Circulating miRNAs, especially serum-based profiles, are highly promising as non-invasive diagnosis in ovarian cancer. Standardization of protocols and prospective validation is necessary for clinical application.

This study aims to provide an updated systematic review on the clinicopathological features, treatment modalities and survival outcomes on SMARCB1-deficient sinonasal carcinoma.

Pituitary neuroendocrine tumours (PitNETs) range from slow-growing to highly aggressive tumours; however, traditional prognostic markers often fail to predict clinical outcomes reliably. DNA methylation has recently emerged as a promising biomarker for assessing tumour behaviour. This systematic review evaluates its predictive value in PitNETs. To systematically assess the clinical applicability of DNA methylation profiles in predicting behaviour of PitNETs. Systematic review. A comprehensive search was conducted in Medline, Embase, Web of Science, and Cochrane CENTRAL on December 13, 2024, with an update on October 17, 2025. The search included studies on adult PitNET patients, specifically examining tumour behaviour in relation to DNA methylation. Excluded were studies that focused on cell-free DNA, investigated a single gene with no established relevance to tumour behaviour, or assessed tumour size only. Data were extracted from 20 eligible studies by four independent reviewers. The risk of bias was assessed using the QUIPS tool. Due to methodological differences across studies, the findings were summarised narratively. Twelve studies investigated tumour invasiveness, two examined tumour aggressiveness and five examined PitNET regrowth, recurrence and re-intervention. The majority of studies concentrated on non-functioning PitNETs and used Illumina arrays or PCR-based methods. These analyses identified several differentially methylated genes linked to invasiveness (e.g., PHYHD1, WNT4, STAT6, CDH1, CDH13), aggressive behaviour (e.g., AIP, PDCD1, LINE-1), and tumour regrowth (e.g., TERT, FAM90A1, ING2). DNA methylation profiling shows potential for predicting PitNET behaviour, but methodological inconsistencies limit its clinical application. Standardized methods and prospective validation are needed for clinical integration.

Phosphatase and tensin homolog (PTEN) alterations are increasingly encountered on molecular testing of thyroid fine-needle aspiration (FNA) specimens in Bethesda III/IV nodules. Unlike high-specificity alterations (e.g., BRAF V600E), PTEN alterations can map to a broad morphologic spectrum and are influenced by the diagnostic pathway determining which nodules proceed to surgery. We performed a systematic review and meta-analysis to define risk of malignancy (ROM) for PTEN-altered thyroid nodules detected preoperatively.

Urothelial bladder cancer (UBC) carries significant mortality and treatment morbidity. Conventional diagnostic and monitoring methods, including cystoscopy and biopsy, are invasive and limited in sensitivity. Circulating tumor DNA (ctDNA), a minimally-invasive "liquid biopsy," has emerged as a promising tool for real-time disease assessment. This study aimed to systematically evaluate the diagnostic, prognostic, and predictive value of plasma and urine ctDNA in localized, locally advanced, and metastatic UBC.

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.

Breast cancer remains one of the most common types of cancer, including the subtype triple-negative breast cancer (TNBC) which is challenging to treat due to its aggressiveness. Cancer-testis antigens (CTAs), especially New York Esophageal Squamous Cell Carcinoma 1 (NY-ESO-1), have become promising immunotherapeutic targets attributable to their restricted expression profile in normal tissues but overexpressed in TNBC, leading to immunogenicity. This review provides comprehensive discussion of NY-ESO-1 including its structural basis of NY-ESO-1 recognition by T cell receptors (TCRs) and antibodies, epigenetic regulation via DNA methylation or histone modifications, and expression patterns or clinical relevance in TNBC. A systematic meta-analysis of 12 studies comprising 1,545 TNBC patients showed a pooled NY-ESO-1 expression prevalence of 16.1% (95% CI: 11.4-22.2%), with heterogeneity (I2=83.7%) attributable to antibody clone used for NY-ESO-1 detection (E978: 15.1% vs. D8.38: 32.6%, p<0.0001) and scoring methods (composite scoring: 15.9% vs. dual scoring: 16.9% vs. H-score: 10.1% vs. simple threshold: 32.6%, p<0.001). Structural analyses reveal NY-ESO-1157-165 recognition by TCRs, antibodies, and engineered binding scaffolds. We examine preclinical and clinical evidence for NY-ESO-1-targeted therapies, including adoptive cell therapy and peptide vaccines, which show manageable safety profiles and induce immunological responses. Epigenetic regulation is a therapeutic avenue, whereby hypomethylating agents and histone deacetylase inhibitors can upregulate NY-ESO-1 expressions that promote tumor immunogenicity. Nonetheless, challenges persist such as NY-ESO-1 expression heterogeneity, lack of TNBC-specific clinical trials, and inadequate immunogenicity. Future research should standardize NY-ESO-1 detection protocols to identify TNBC patients for NY-ESO-1-targeted immunotherapy, prioritize TNBC-specific trials and combinations with epigenetic priming agents.

Glioma is a malignant cancer that affects the central nervous system. Early detection of glioma is still difficult due to the hard-to-reach location of the cancer. The use of next generation sequencing is one of the new developments that can be used for diagnosis, however the use of this modality for prognosis is still rarely discussed. This systematic review aims to determine the benefits of using next generation sequencing (NGS) on the assessment of ctDNA or cfDNA concentration, progression free survival (PFS), and overall survival (OS). This systematic review was made using data from six databases, namely PubMed, PMC, ProQuest, Google Schoolar, ScienceDirect, and SCOPUS, and was compiled based on guidelines from PRISMA. Fourteen studies were included in this systematic review with a total of 663 glioma patients. The results of ctDNA measurements generated through the NGS method with liquid biopsy samples show that the higher the grading and sampling when the tumor progresses can increase the ctDNA value. When assessing ctDNA concentrations at baseline when samples were taken, most studies showed a worse prognosis for PFS and OS survival time. However, the grouping of patients in the current studies is still highly variable so further studies with standardized ctDNA cut off values are needed for more precise determination of prognosis.

Somatic mutation testing in solid tumours represents a rapidly advancing field which increases opportunities for access to molecularly targeted therapeutics and clinical trials. This systematic review determined whether socio-demographic inequalities affect utilisation of novel somatic mutation testing.

Cerebral Cavernous Malformations (CCMs) are low-flow vascular lesions located within the central nervous system, with a reported prevalence in the general population of 0.16-0.5%. Patients with CCMs may remain asymptomatic or present new onset symptoms such as seizures or focal neurological deficits often related to the occurrence of intracerebral hemorrhage. CCM may appear sporadic or as part of familial forms linked to mutations in the CCM-gene cluster, affecting endothelial cell integrity and triggering molecular cascades, including the MEKK3/KLF2/4 signaling pathway. Recent studies have highlighted the roles of inflammatory, angiogenic, and coagulation pathways alongside the emerging evidence of a gut-brain axis influencing microbiome-driven TLR4 signaling. This systematic review aims to describe molecular biomarkers associated with CCM pathophysiology, emphasizing their potential use as diagnostic and prognostic tools. Circulating plasma biomarkers such as CRP, vitamin D, and interleukins may reflect ongoing inflammatory and endothelial processes, while some imaging biomarkers like Quantitative Susceptibility Mapping (QSM) have shown a correlation with iron deposition and vascular leakage. Leveraging both circulating and imaging biomarkers may improve the therapeutic decision-making process. Further studies are encouraged to validate these findings and to facilitate the development of personalized, evidence-based strategies for the management of CCM.

Adult-type gliomas are among the most prevalent and lethal primary central nervous system tumors, where prompt and accurate diagnosis is essential for maximizing survival prospects. Molecular classification, particularly the detection of isocitrate dehydrogenase (IDH) mutations and 1p/19q codeletions, has become crucial for accurate diagnosis and prognosis. Artificial intelligence (AI) has emerged as a promising adjunct in enhancing diagnostic accuracy using histopathological images. Existing reviews mostly focused on radiology rather than histopathology, and no comprehensive systematic review has specifically evaluated AI performance exclusively from histopathological images for detecting these two molecular markers.

Current diagnostic pathways for prostate cancer have unsatisfactory specificity (SPE) and rely heavily on magnetic resonance imaging, underscoring the need for novel diagnostic biomarkers. This article provides a systematic review of the evidence on using blood-derived cell-free DNA (cfDNA)-based biomarkers for prostate cancer diagnosis. A structured review was conducted according to the Preferred Items for Systematic Reviews and Meta-Analyses guidelines. Original peer-reviewed research articles published before August 2025 were identified from PubMed/Medline, Web of Science, and Embase using keyword combinations related to prostate cancer, cfDNA, and diagnostic test performance. Studies that compared blood-derived cfDNA-based diagnostic biomarkers in men with and without prostate cancer were included. Fifty-nine articles were identified and analyzed. Most articles reported qualitative cfDNA assays relying on PCR (N = 37) or next-generation sequencing (NGS; N = 10). Diagnostic test performance improved for aggressive and metastatic prostate cancer. However, evidence about clinical validity in localized disease is scarce, particularly for NGS-based methods (three studies). GSTP1 promoter hypermethylation, the most frequently investigated biomarker, showed an average sensitivity and SPE of 35.1% and 91.2%, respectively, for the detection of localized prostate cancer. Overall, circulating tumor DNA represents a promising diagnostic biomarker for prostate cancer early detection. High-quality discovery and validation research in the intended-use setting are essential to fully understand clinical validity and utility.

Epidermal growth factor receptor (EGFR) mutations are major oncogenic drivers in non-small cell lung cancer (NSCLC), occurring in 30-50% of Asian patients. Neoadjuvant EGFR-tyrosine kinase inhibitors (EGFR-TKIs) may improve surgical outcomes in resectable EGFR-mutant NSCLC, but evidence from small, heterogeneous trials is inconsistent and the overall efficacy and safety remain unclear.

BACKGROUND: The breast cancer (BC) susceptibility genes 1 (BRCA1) and BC susceptibility genes 2 (BRCA2) are critical genes associated with hereditary breast cancer, and their mutation prevalence might greatly vary across different ethnic populations. This systematic review and meta-analysis evaluated global ethnic variation in BRCA1/2 mutation prevalence among breast cancer (BC) patients. METHODS: We searched five databases for studies published between 2015 and 2025 that reported BRCA1/2 mutations in BC patients across various ethnic groups. 45 studies met the inclusion criteria, comprising about 44,000 BC patients. Data were stratified into two categories: (1) the frequency of all reported variants (including high-frequency polymorphisms) to assess global reporting patterns, and (2) the estimated clinical prevalence of confirmed Pathogenic and Likely Pathogenic (PLP) variants (excluding benign polymorphisms) for cancer risk assessment in broad ethnic categories (Asian, Chinese, Black/African descent, Hispanic/Latino, Middle Eastern/North African, European, Ashkenazi Jewish, and others). RESULTS: The prevalence of BRCA1/2 mutations in BC patients displayed substantial global variability. Heterogeneity was high (I² >95%, p < 0.001), reflecting diverse study populations and designs. The frequency of all reported variants varied substantially, reaching up to 17% in specific subgroups due to the inclusion of common polymorphisms. However, after strict filtering, the clinical prevalence of PLP variants ranged from < 1% to 5% in most ethnic groups, aligning with expected population risk. CONCLUSION: Ethnicity significantly influences BRCA1/2 mutation distribution among BC patients globally. These findings underscore the importance of population-tailored genetic testing approaches and the necessity of including underrepresented groups in genetic research to enhance risk assessment and personalized cancer care.

Primary breast neuroendocrine tumors (BNETs) are rare malignancies recently redefined by the World Health Organization (WHO) 2019 classification, which mandates neuroendocrine morphology in over 90% of tumor cells. This systematic review aims to provide the first comprehensive analysis of BNETs strictly adhering to these diagnostic criteria.

Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein 9 (CRISPR/Cas9) technology has become a revolutionary tool in medicine, offering substantial potential for treating a wide range of diseases, including hematological disorders, cancers, genetic conditions, and ophthalmological diseases. This systematic review evaluates the efficacy, safety, and applicability of CRISPR/Cas9 in clinical trials. A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane databases was conducted. All studies, up to November 2024, meeting the eligibility criteria assessing the application of CRISPR for the treatment of diseases were included. A quality assessment of the included studies was conducted using the Cochrane risk of bias tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement for systematic reviews and meta-analyses was followed, and a total of 17 studies were included. This systematic review of CRISPR/Cas9 technology focused on its effectiveness and safety across various diseases. In nonmalignant hematological disorders, CRISPR successfully treated β-thalassemia and sickle cell disease, resulting in high transfusion independence and the elimination of disease crises. In malignant hematological disorders, B-cell acute lymphoblastic leukemia, CRISPR-engineered chimeric antigen receptor T (CAR-T) cells achieved an 83.3% complete remission rate. Furthermore, CRISPR-based CAR-T cells showed promising results in B-cell non-Hodgkin's lymphoma. In oncology, lung cancer and other solid tumors are among the diseases that have been safely engineered using CRISPR gene editing technology. For genetic disorders, CRISPR improved vision in retinal degeneration and reduced symptoms in hereditary angioedema and transthyretin amyloidosis with mild side effects. The results demonstrated CRISPR's potential across a wide range of conditions. In conclusion, the findings underscore the potential role of CRISPR/Cas9 technology across a wide range of diseases. However, challenges remain, including optimizing delivery systems, minimizing off-target effects, addressing immunogenicity concerns, and ethical considerations.