Immunotherapy has become the first-line treatment for metastatic mismatch repair deficient (dMMR) colorectal cancer. The efficacy and safety of neoadjuvant immunotherapy for the treatment of non-metastatic dMMR colorectal cancer remain unclear. In this article, we explore the clinical effect and safety of neoadjuvant immunotherapy for non-metastatic dMMR colorectal cancer.

While there is a growing volume of evidence suggesting that relatively prevalent functional polymorphisms present within apoptosis-related genes may influence human prostate cancer (PCa) susceptibility, the clinical relevance of these findings remains inconclusive.

Aberrations in the regulatory genome play a pivotal role in population-level disease predisposition. Annotation of the regulatory regions using appropriate primary tissues - instead of cell lines affected by selection and other confounding factors - could shed new light into mechanisms underlying common conditions. We test this approach in uterine leiomyomas, highly prevalent benign neoplasms of the myometrium, by creating 15-state chromatin annotations for myometrium and uterine leiomyomas. Integration with RNA-seq, ATAC-seq, HiChIP and methylation data enables us to compare the epigenomes of myometrium and ULs with distinct driver mutations, highlighting the role of bivalent regions in the neoplastic process. Subsequently, a genome wide association study meta-analysis is performed, using three different cohorts. Disease association loci are enriched at active chromatin, especially at enhancers, and harbor tumor- and driver mutation-specific chromatin states. At SATB2 locus we show the effect of the risk genotype already in the normal tissue. Integration of genome-wide association studies and deep regulatory genomics data from the correct tissue type represents a powerful approach in understanding population-level disease predisposition.

In the last twenty years, epidemiological research has suggested a potential decreased susceptibility to cancer among individuals diagnosed with Parkinson's disease (PD), although conflicting findings exist regarding the connection between PD and Colorectal cancer (CRC). This systematic review and meta-analysis were conducted to investigate the contemporary epidemiological data on the risk of CRC in PD.

Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of pneumothorax. This study aimed to determine the prevalence of spontaneous pneumothorax among individuals diagnosed with BHD syndrome.

Several observational studies have reported epidemiologic associations between psoriasis and risk of some cancers, but systematic evidence is lacking. Our aim was to comprehensively estimate the association between psoriasis and the risk of 33 common cancers using systematical Mendelian randomization based on genetic data.

Glioblastoma (GBM) is the most aggressive and heterogeneous neoplasm among central nervous system tumors, with a dismal prognosis and a high recurrence rate. Among the various genetic alterations found in GBM, the amplification of epidermal growth factor receptor (EGFR) and the EGFR variant III (EGFRvIII) mutation are among the most common, though their prognostic value remains controversial. This systematic review and meta-analysis aimed to provide a comprehensive evaluation of the diagnostic and prognostic significance of EGFR amplification and the EGFRvIII mutation in GBM patients, incorporating recent studies published in the past few years to offer a more complete and up-to-date analysis. An extensive search of the PubMed, Web of Science, and Scopus databases was conducted, including studies that reported on EGFR and/or the EGFRvIII mutation status with detailed survival data. A total of 32 studies with 4208 GBM patients were included. The results indicated that EGFR amplification significantly correlated with worse OS (Overall survival) (HR = 1.27, 95% CI: 1.03-1.57), suggesting that EGFR amplification is an independent prognostic marker. The prognostic value of EGFRvIII was inconclusive, with a pooled hazard ratio for overall survival of 1.13 (95% CI: 0.94-1.36), indicating no significant effect on survival in the general population. However, a subgroup analysis suggested that EGFRvIII may be associated with poorer outcomes, particularly in recurrent GBM patients, where its prognostic significance became more evident. Furthermore, subgroup analyses based on geographic region revealed significant heterogeneity in the prognostic impact of EGFR amplification across different populations. In American cohorts, EGFR amplification was strongly associated with an increased risk of mortality (HR = 1.53, 95% CI: 1.28-1.84, p = 0.001), suggesting that it serves as a more reliable prognostic marker in this region. In contrast, no significant prognostic impact of EGFR amplification was observed in Asian (HR = 0.64, 95% CI: 0.35-1.17) or European (HR = 0.98, 95% CI: 0.80-1.19) populations. Overall, this study underscores the potential of EGFR amplification as a prognostic marker in GBM, while further research is needed to fully elucidate the role of the EGFRvIII mutation, particularly in specific patient subgroups. Clarifying these associations could offer important insights for targeted treatment strategies, improving patient outcomes.

Background: The relationship between autoimmune diseases (AIDs) and cancer is unclear and this study aimed to investigate the relationship between AIDs and cancer at the genetic level using Mendelian randomization (MR). Methods: The study employed two-sample MR and meta-analysis to investigate the association between AIDs and 33 types of cancer, following STROBE-MR guidelines. Single nucleotide polymorphisms (SNPs) associated with AIDs were used as instrumental variables, with data from FinnGen, UK Biobank, and other databases. MR analyses included sensitivity checks, heterogeneity assessments, and reverse causality tests, using multiple MR methods (inverse-variance weighted (IVW), weighted median, MR-Egger, etc.). Meta-analysis was performed on validated results to confirm findings, with statistical analyses conducted using R software. Results: The results identified eight significant associations in both discovery and replication stages. Key findings include that myasthenia gravis (MG) significantly increases the risk of oral cavity cancer, multiple sclerosis (MS) is linked to increased risks of chronic lymphocytic leukemia (CLL) and small intestine cancer, and ulcerative colitis (UC) has mixed effects, reducing the risk of uterine cervix and larynx cancers, but increasing risks for pancreatic and bladder cancers. Meta-analysis confirmed eight secondary findings, highlighting pathogenic associations such as type 1 diabetes with esophagus cancer and protective effects like systemic lupus erythematosus (SLE) against acute myelocytic leukemia. Conclusions: This study provides evidence of a causal relationship between multiple AIDs and different cancer risks at the genetic level and provides a reference for the health management of patients with AIDs.

The combination of traditional Chinese medicine (TCM) with chemotherapy has been widely applied in the treatment of gastric cancer (GC). However, previous clinical studies have been constrained by small sample sizes and a lack of investigation into the molecular mechanisms of TCM. This study aims to assess the efficacy of TCM in treating GC by leveraging the strengths of meta-analysis and multi-omics approaches while also summarizing the underlying pharmacological mechanisms.

Epidermal growth factor receptor (EGFR) mutations are present in 10-60% of all non-small cell lung cancer (NSCLC) patients and are associated with dismal prognosis. Lung cancer brain metastases (LCBM) are a common complication of lung cancer. Predictions of EGFR can help physicians in decision-making and, through optimizing treatment strategies, can result in more favorable outcomes. This systematic review and meta-analysis evaluated the predictive performance of machine learning (ML)-based models in EGFR status in NSCLC patients with brain metastasis.

The telomerase reverse transcriptase (TERT) promoter mutations have been linked to the prognosis and survival of several cancers; however, it is still debatable in case of oral squamous cell carcinoma. The exact reason for it is currently unknown. However, considering its role in cell survival and proliferation it is imperative to evaluate the association between TERT promoter mutations and OSCC. The systematic review and meta-analysis were carried out to gather evidence for TERT promotor mutation in OSCC. Electronic databases along with grey literature were searched for relevant studies. We used fixed- or random-effect models to calculate pooled proportion, estimated odds ratios or standardized mean differences, and corresponding 95% confidence intervals (CIs). We included 13 eligible studies incorporating 816 cases. The average frequency of TERT promotor mutation was 46.1% (0.46, 95% CI, 0.33, 0.60). However, TERT promoter mutations were not associated with gender, habit (smoking and betel nut), nodal involvement, metastases, and TNM stage. C228T (189/287), C250T (73/287), C228A, and other variants of TERT mutation were frequently detected TERT mutation variant in OSCC. TERT promoter mutations could be considered as biomarkers assisting in risk stratification and prognostic prediction.

to compare the diagnostic accuracy of DNA ploidy compared to biopsy followed by histopathological investigation in patients with oral potentially malignant disorders (OPMDs).

Artificial intelligence (AI) networks offer significant potential for predicting immunotherapy outcomes in gastrointestinal cancers by analyzing genetic mutation profiles. Their application in prognosis remains underexplored. This systematic review and meta-analysis aim to evaluate the effectiveness of AI-based models, which refers to systems utilizing artificial intelligence to analyze data and make predictions, in predicting immunotherapy responses in gastrointestinal cancers using genetic mutation features.

The combined therapy strategy of venetoclax with hypomethylating agents (HMAs) has demonstrated encouraging efficacy in the treatment of acute myeloid leukemia (AML), particularly in elderly patients or those deemed unfit for standard treatments. However, due to differences in the research focuses of various research centers, the results have not yet comprehensively and systematically demonstrated the clinical significance of this treatment approach. Therefore, in this meta-analysis, we aimed to assess the effectiveness and safety of venetoclax in combination with HMAs for the treatment of AML. We included a total of 20 clinical studies that met the search criteria, including research focused on AML patients carrying FLT-3 and IDH mutations. Results revealed an overall response (OR) rate of 0.57 and a complete remission (CR)/complete remission with incomplete marrow recovery (CRi) rate of 0.52. Subgroup analyses indicated varying CR/CRi rates among patients with different genetic mutations, with the highest rate observed in IDH mutation carriers at 0.71, FLT-3 mutation carriers at 0.64, and TP53 mutation carriers at 0.44. Simultaneously, we observed adverse events such as anemia, neutropenia, and thrombocytopenia, underscoring the importance of careful management during venetoclax and HMAs treatment. This study emphasizes the potential of venetoclax and HMAs as a promising therapeutic approach for AML while highlighting the critical need for monitoring and managing adverse events in such treatment regimens.

The prognostic significance of KRAS and BRAF mutations is well-established in metastatic colorectal cancer (CRC) but remains uncertain in early-stage tumors. This study retrospectively analyzed 47 stage II/III CRC patients undergoing curative surgery to assess the association of mutations in KRAS, NRAS, BRAF, and PIK3CA with overall survival (OS) and disease-free survival (DFS). Additionally, a meta-analysis was conducted to validate the prognostic relevance of these gene mutations. We included post hoc analyses of phase III randomized controlled trials (RCTs) in stage II/III patients receiving adjuvant therapy after curative resection in the meta-analysis. Pooled hazard ratio (HR) and 95% confidence interval (CI) was calculated using a random-effect model in the overall population, stratified subgroups adjusted for microsatellite instability (MSI) status, and within MSI-high (MSI-H) and microsatellite-stable (MSS) populations. In the retrospective cohort, mutations in KRAS, NRAS, BRAF, and PIK3CA were identified in 29.8%, 4.3%, 8.5%, and 14.9% of patients, respectively. No significant association between individual genes and survival was observed. However, in MSS patients, concurrent mutations were significantly associated with shorter OS and DFS (log-rank test, P < 0.05). The meta-analysis incorporated 13 eligible studies, including 15,034 patients. Pooled analyses revealed that KRAS and BRAF mutations were significantly linked to poor OS (KRAS: HR = 1.25, 95%CI: 1.06-1.47, P = 0.008; BRAF: HR = 1.43, 95%CI: 1.26-1.63, P < 0.001) and DFS (KRAS: HR = 1.36, 95%CI: 1.21-1.53, P < 0.001; BRAF: HR = 1.21, 95%CI: 1.02-1.44, P = 0.032). The prognostic impact of BRAF mutation increased with MSI adjustment compared those without MSI adjustment. In MSS tumors, KRAS-mutant patients demonstrated significantly shorter DFS (HR = 1.63, 95%CI: 1.25-2.13, P < 0.001), while BRAF-mutant patients exhibited reduced OS (HR = 1.53, 95%CI: 1.24-1.89, P < 0.001) and DFS (HR = 1.72, 95%CI: 1.20-2.46, P = 0.003) compared to wildtype patients. Conversely, no significant survival differences were found between mutant and wildtype patients in the MSI-H population. Although PIK3CA mutation was nominally associated with OS (HR = 0.86, 95%CI: 0.75-1.00, P = 0.046), the pooled result lacked robustness. In conclusion, KRAS and BRAF mutations had a negative prognostic impact on MSS stage II/III CRC patients receiving adjuvant therapy following curative resection. These patients may benefit from more effective adjuvant treatment strategies.

This meta-analysis evaluates the diagnostic value of SOX1 methylation across different cervical cancer types, including squamous cell carcinoma and adenocarcinoma, to assess its efficacy as a biomarker.

Acquired MET alterations is one of the resistance mechanisms to advanced NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKIs). Several clinical trials combined MET-TKI (such as capmatinib, tepotinib, savolitinib) with EGFR-TKI to overcome MET alterations resistance. We performed this meta-analysis to determine the efficacy and safety of MET-TKI plus EGFR-TKI combined therapy in NSCLC patients.

Multiple myeloma ranks as the second most common hematopoietic malignancy in terms of both incidence and mortality. Prognostic stratification is critical for optimizing therapeutic strategies, as certain genetic alterations can significantly influence disease progression and treatment response. The meta-analysis analyzed data from 3421 multiple myeloma patients and 14,720 controls. PubMed, Web of Science, and Scopus were used as databases. Associations between the SNPs and multiple myeloma were calculated as a measure of pooled odds ratios (ORs) and 95% confidence intervals. Statistical analysis was performed using Review Manager (RevMan). DNAH11 rs4487645 A/C genotype (OR = 1.35; 95% CI: 1.24-1.46; p < 0.00001; I2 = 0%), ULK4 rs1052501 G/G genotype (OR = 1.21; 95% CI: 0.98-1.50; p = 0.08; I2 = 64%), ULK4 rs1052501 A/G genotype (OR = 1.23; 95% CI: 1.13-1.34; p < 0.00001; I2 = 0%), DTNB rs6746082 A/A genotype (OR = 1.10; 95% CI: 1.01-1.20; p = 0.03; I2 = 45%), and VDR rs1544410 A/G genotype (OR = 1.87; 95% CI: 1.04-3.36; p = 0.04; I2 = 0%) increased multiple myeloma risk. Our study concludes that DNAH11, ULK4, DTNB, and VDR may serve as predictive biomarkers for MM risk.

B7H3 (CD276), an immunoregulatory molecule known for its role in immune evasion by transmitting inhibitory signals to T lymphocytes, has garnered significant attention in recent years as a promising target for cancer immunotherapy. This interest is largely due to its high expression in various types of solid tumors, coupled with low protein levels in normal tissues. However, studies examining the impact of B7H3 on survival outcomes have shown inconsistent results, leaving its prognostic significance not fully clarified. Therefore, this meta-analysis aimed to assess the relationship between B7H3 expression and various prognostic parameters in patients with solid malignancies. PubMed, Web of Science (WOS), Cochrane, SCOPUS, and Embase databases were searched for eligible articles published until November 2024. Statistical analysis was performed using R studio (version 4.3.2). The analysis included a total of 51 eligible studies comprising 11,135 patients. Results showed that overexpression of B7H3 is a negative predictor for all examined survival outcomes: OS (HR = 1.71, 95% CI = 1.44-2.03, p < 0.0001), DFS (HR = 2.02, 95% CI = 1.49-2.73, p < 0.0001), PFS (HR = 2.10, 95% CI = 1.44-3.06, p < 0.0001), RFS (HR = 1.66, 95% CI = 1.11-2.48, p = 0.01), and DSS (HR = 1.70, 95% CI = 1.24-2.32, p < 0.01). Despite the high heterogeneity observed across the studies, the sensitivity analysis confirmed the robustness of these results. This research suggests that B7H3 may serve as an effective biomarker for prognosis in solid tumors.

Angiopoietin-like protein 4 (ANGPTL4) plays a crucial role in processes such as angiogenesis, inflammation, and metabolism. Despite numerous studies suggesting its involvement in cancer, a definitive role remains unclear. We introduce the first comprehensive meta-analysis and pan-cancer bioinformatics study on ANGPTL4, aiming to unravel its implications across various cancer types.