Integrated pan-cancer analysis of CSMD2 as a potential prognostic, diagnostic, and immune biomarker

Abstract

The protein encoded by CUB and Sushi Multiple Domains 2 (CSMD2) is likely involved in regulating the complement cascade reaction of the immune system. However, current scientific evidence on the comprehensive roles of CSMD2 in pan-cancer is relatively scarce. Therefore, in this study, we explored the transcriptional level of CSMD2 in pan-caner using TCGA, GEO, and International Cancer Genome Consortium databases. Receiver operating characteristic curve analysis was used to investigate the diagnostic efficacy of CSMD2. The Kaplan-Meier Plotter and Oncolnc were used to investigate the correlation between CSMD2 expression and prognosis. Additionally, we analyzed the correlation between epigenetic methylation and CSMD2 expression in various cancers based on UALCAN, as well as, the correlation between CSMD2 and tumor mutational burden (TMB), microsatellite instability (MSI), and tumor neoantigen burden (TNB) in tumors. TIMER2.0 database was employed to investigate the correlation between CSMD2 and immune cells in the tumor microenvironment and immune checkpoints. Based on TISIDB, the correlation between CSMD2 and MHC molecules and immunostimulators was analyzed. Ultimately, we observed with a pan-cancer analysis that CSMD2 was upregulated in most tumors and had moderate to high diagnostic efficiency, and that high expression was closely associated with poor prognosis in patients with tumors. Moreover, hypermethylation of CSMD2 promoter and high levels of m6A methylation regulators were also observed in most cancers. CSMD2 expression was negatively correlated with TMB and MSI in stomach adenocarcinoma (STAD) and stomach and esophageal carcinoma (STES), as well as with tumor mutational burden, microsatellite instability, and TNB in head-neck squamous cell carcinoma (HNSC). In most cancers, CSMD2 might be associated with immune evasion or immunosuppression, as deficient anti-tumor immunity and upregulation of immune checkpoints were also observed in this study. In conclusion, CSMD2 could serve as a promising prognostic, diagnostic and immune biomarker in pan-cancer.

Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing

“…In this family, in addition to the strong candidate variant in NKD1 and the pathogenic mutation in a functional domain of the TC-gene TG [75], we also found four variants in the genes ROBO1, MYH10, CSMD2 and STK32A, all of them with a positive expression in thyroid cancer according to public databases, suggesting that they could play a role in familial NMTC development. Whereas changes in the expression of the MYH10, CSMD2 and STK32A have been reported in other tumors causing alterations in cell proliferation [76][77][78], the gene ROBO1 has a significant association with the regulation of nervous system development [79]. It is noteworthy that, beyond the variant in the Wnt-related gene GGNBP2, two other variants were found in the NMTC_6 family, which were also implicated in this biological function (Figure 2F): RNF20, an E3 ligase of H2BK120 regulating astrocyte production from neural precursor cells [80] and HOOK3, which mediates binding between microtubules and organelles, important for maintaining genomic integrity and for the maintenance of proper centrosome function in neural cells [81,82].…”

Pharmacogenomics of intravenous immunoglobulin response in Kawasaki disease

“…MHC-II molecules present exogenous antigenic peptides to CD4+ T-cells, which activate CD4+ helper T-cells. CSMD2 expression was also negatively correlated with infiltration of anti-tumor immune cells, including macrophages and natural killer cells, and was positively associated with immune evasion ( 63 ). Thus, for patients with Kawasaki disease, a mutation altering CSMD2 may promote a hyper inflammatory response.…”

Overview of distinct N6-Methyladenosine profiles of messenger RNA in osteoarthritis

“…Accumulating evidence indicates that m6A modification participates in the regulation of critical biological processes and pathogenesis of numerous human diseases ( Zhao et al, 2020 ; Jiang et al, 2021 ). A variety of m6A-modified mRNAs have the potential to serve as novel biomarkers for diagnosis or therapeutic targets for chemotherapy ( Ianniello et al, 2019 ; Liu K. et al, 2022 ; Zhang H. et al, 2022 ; Qiu et al, 2022 ). Furthermore, the importance of m6A modification is underscored by its evolutionary conservation across species and its presence in all eukaryotic organisms.…”