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.

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.

Leptomeningeal disease (LMD) is a devastating complication of advanced solid tumors with limited prognostic and response-assessment tools. Because LMD molecular evolution is frequently compartmentalized behind CNS barriers, cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) may provide CNS-specific molecular readouts of disease activity. We evaluated whether baseline CSF ctDNA profiles and longitudinal ctDNA kinetics associate with survival in LMD.

Germline biomarker testing to assess inherited risk for developing malignancy has evolved quickly from testing for 1 or 2 genes from a few laboratories to ordering panels of 80 or more genes available from multiple laboratories. Many health professionals did not receive foundational information in training yet are expected to identify and manage care for individuals and families with germline risk. Errors in testing do occur and can have significant adverse consequences including missed opportunities for prevention and detection for the patient and family, unnecessary risk-reducing surgery, and even death. By better understanding these errors and underlying causes, as well as the potential negative consequences due to these errors, strategies can be developed to help prevent future harm to patients.

Decitabine (DEC) and Venetoclax (VEN) are approved for elderly adult acute myeloid leukemia (AML) patients with an additional sex comb-like 1 (ASXL1) mutation who cannot tolerate intensive chemotherapy. However, direct comparative data in this population remain limited. A systematic review and meta-analysis were conducted to assess the indirect efficacy of DEC alone and VEN in older AML patients with ASXL1 mutations. A matched cohort was created by comparing outcomes of consecutive adults with AML who received DEC or DEC with VEN after propensity score matching using the nearest-neighbor methodology. The DEC + VEN cohort had a lower early mortality rate than the DEC cohort (30-day mortality: 2.7%-5% vs. 9.7%, p = 0.01; RR = 0.90, 95% CI 0.83-0.97 versus RR = 0.97, 95% CI 0.92-1.02). However, the 30-day and 60-day mortality rates were similar between groups (9.5% vs. 2.7%, p = 0.17; 18.9% vs. 9.5%, p = 0.16). Overall survival (OS) was measured at 7.9-25.1 months. The DEC + VEN cohort had significantly higher response rates than the decitabine cohort. According to the 2017 EL N Genetic Risk classification, people with a favorable moderate risk had a higher rate of complete response or complete response with incomplete hematologic recovery than those with high risk (65% vs. 34%). The use of DEC for 5 or 10 days as the hypomethylating agents combination with VEN did not affect the CR/Cri rate. In conclusion, DEC plus VEN was associated with improved clinical responses and survival signals in ASXL1-mutated AML, warranting prospective confirmation.

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.

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.

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.

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.

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.

Human epidermal growth factor receptor 2 (HER2)-targeted therapies have been investigated for therapeutic benefit in RAS/BRAF wild-type/HER2+ metastatic colorectal cancer (mCRC). Unlike HER2+ breast and gastric cancer, there are no regulatory criteria for determining HER2 overexpression in patients with mCRC. This systematic literature review describes unmet needs for patients with HER2+ mCRC in relation to testing and treatment, highlights the importance of early HER2 testing at mCRC diagnosis, and discusses the evolving treatment landscape. We utilised PubMed and EMBASE databases up to November 2023 to identify journal articles and published congress abstracts relating to the HER2+ disease and treatment landscape, HER2 testing in mCRC, and HER2-targeted treatments in mCRC. Many studies have demonstrated the utility of immunohistochemistry, in situ hybridisation, and next-generation sequencing (tissue- and circulating tumour DNA-based) for detecting HER2 overexpression/amplification in mCRC and have attempted to establish consolidated criteria like those used for breast and gastric cancer. The value of HER2-targeted treatments in patients with HER2+ mCRC has been evidenced by clinical trials and meta-analyses, with strong evidence from MOUNTAINEER and DESTINY-CRC01 which supports the use of tucatinib + trastuzumab or trastuzumab deruxtecan, respectively, among this patient population. However, real-world analyses have confirmed that patients with HER2+ mCRC are not routinely tested for HER2 overexpression. Strong evidence and clinical guidelines support the value of HER2-targeted treatment among patients with HER2+ mCRC. There is a need for increased awareness and earlier uptake of HER2 testing among patients with mCRC to broaden treatment options and optimise outcomes for this patient population.