Gene expression and DNA methylation analyses suggest that two immune related genes are prognostic factors of colorectal cancer

Abstract

Background Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC. Methods In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model. Results Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers. Conclusion This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.

Identification of the prognostic signature based on genomic instability-related alternative splicing in colorectal cancer and its regulatory network

“…Among these SFs, HSPA1A and FAM50B were associated with OS in CRC. We found that patients with lower HSPA1A expression levels had higher OS rates, which was consistent with previous studies ( Xing et al, 2021 ). As a member of the heat shock proteins (HSPs) family, heat shock protein family A (Hsp70) member 1A (HSPA1A) exerted cytoprotective and immunological functions ( Wang et al, 2021 ).…”

Identification of the Prognostic Significance of a Somatic Mutation-derived Alternative Splicing Signature in Colorectal Cancer

“…Among these splicing factors, HSPA1A and FAM50B were associated with OS in CRC. We found that patients with higher HSPA1A expression had reduced OS rates, consistent with previous study (Xing et al 2021). As a member of the heat shock proteins (HSPs) family, heat shock protein family A (Hsp70) member 1A (HSPA1A) exerted cytoprotective and immunological functions (Schmitt et al 2007).…”

Immune-Related lncRNAs to Construct Novel Signatures and Predict the Prognosis of Rectal Cancer

“…Previous studies indicated that OS-related genes could be used to construct the risk assessment model. According to previous studies, we also constructed a risk assessment model by using those three IR-DELs (C17orf77, GATA2-AS1, and TPT1-AS1) (18,19). The correlation analysis results showed that risk value was correlated with pathologic N, pathologic M, pathologic stage, several immune cells, and immune factors.…”

“…The risk model was established based on the expression data and multiplied Cox regression coefficients. The formula was set as followed, risk score = expression level of C17orf77 * (−1.5905) + expression levels of GATA2-AS1 * (−1.3003) + expression level of TPT1-AS1 * (−1.4072) (18,19). To further investigate the relevance of the risk model with the clinical pathological features of READ, we analyzed the relationship between the risk value and vital status, gender, pathologic NMT, and pathologic stage.…”