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Recent studies have highlighted the biological significance of RNA N 6 -methyladenosine (m 6 A) modification in tumorigenicity and progression. However, it remains unclear whether m 6 A modifications also have potential roles in immune regulation and tumor microenvironment (TME) formation. Methods : In this study, we curated 23 m 6 A regulators and performed consensus molecular subtyping with NMF algorithm to determine m 6 A modification patterns and the m 6 A-related gene signature in colon cancer (CC). The ssGSEA and CIBERSORT algorithms were employed to quantify the relative infiltration levels of various immune cell subsets. An PCA algorithm based m 6 Sig scoring scheme was used to evaluate the m 6 A modification patterns of individual tumors with an immune response. Results : Three distinct m6A modification patterns were identified among 1307 CC samples, which were also associated with different clinical outcomes and biological pathways. The TME characterization revealed that the identified m 6 A patterns were highly consistent with three known immune profiles: immune-inflamed, immune-excluded, and immune-desert, respectively. Based on the m 6 Sig score, which was extracted from the m 6 A-related signature genes, CC patients can be divided into high and low score subgroups. Patients with lower m 6 Sig score was characterized by prolonged survival time and enhanced immune infiltration. Further analysis indicated that lower m 6 Sig score also correlated with greater tumor mutation loads, PD-L1 expression, and higher mutation rates in SMGs (e.g., PIK3CA and SMAD4 ). In addition, patients with lower m 6 Sig scores showed a better immune responses and durable clinical benefits in three independent immunotherapy cohorts. Conclusions : This study highlights that m 6 A modification is significantly associated with TME diversity and complexity. Quantitatively evaluating the m 6 A modification patterns of individual tumors will strengthen our understanding of TME characteristics and promote more effective immunotherapy strategies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Gastric cancer (GC) is a common tumour that affects humans worldwide, is highly malignant and has a poor prognosis. Small extracellular vesicles (sEVs), especially exosomes, are nanoscale vesicles released by various cells that deliver bioactive molecules to recipient cells, affecting their biological characteristics, changing the tumour microenvironment and producing long-distance effects. In recent years, many studies have clarified the mechanisms by which sEVs function with regard to the initiation, progression, angiogenesis, metastasis and chemoresistance of GC. These molecules can function as mediators of cell-cell communication in the tumour microenvironment and might affect the efficacy of immunotherapy. Due to their unique physiochemical characteristics, sEVs show potential as effective antitumour vaccines as well as drug carriers. In this review, we summarize the roles of sEVs in GC and highlight the clinical application prospects in the future. [ABSTRACT FROM AUTHOR]

Monoubiquitination of FANCD2 is a central step in the activation of the Fanconi anemia (FA) pathway after DNA damage. Defects in the FA pathway centered around FANCD2 not only lead to genomic instability but also induce tumorigenesis. At present, few studies have investigated FANCD2 in tumors, and no pan-cancer research on FANCD2 has been conducted. We conducted a comprehensive analysis of the role of FANCD2 in cancer using public databases and other published studies. Moreover, we evaluated the role of FANCD2 in the proliferation, migration and invasion of lung adenocarcinoma cells through in vitro and in vivo experiments, and explored the role of FANCD2 in cisplatin chemoresistance. We investigated the regulatory effect of FANCD2 on the cell cycle of lung adenocarcinoma cells by flow cytometry, and verified this effect by western blotting. FANCD2 expression is elevated in most TCGA tumors and shows a strong positive correlation with poor prognosis in tumor patients. In addition, FANCD2 expression shows strong correlations with immune infiltration, immune checkpoints, the tumor mutation burden (TMB), and microsatellite instability (MSI), which are immune-related features, suggesting that it may be a potential target of tumor immunotherapy. We further found that FANCD2 significantly promotes the proliferation, invasion, and migration abilities of lung adenocarcinoma cells and that its ability to promote cancer cell proliferation may be achieved by modulating the cell cycle. The findings indicate that FANCD2 is a potential biomarker and therapeutic target in cancer treatment by analyzing the oncogenic role of FANCD2 in different tumors. • This study provides the first pan-cancer analysis of FANCD2 using data from public databases. • FANCD2 is upregulated and has poor prognosis in most cancers and plays a potential role in regulating tumor immunity. • We further validated FANCD2 as an important oncogenic gene and promotes tumor progression by regulating cell cycle. [ABSTRACT FROM AUTHOR]