RNA methylation-related genes INHBB and SOWAHA are associated with MSI status in colorectal cancer patients and may serve as prognostic markers for predicting immunotherapy efficacy

结直肠癌 甲基化 列线图 微卫星不稳定性 DNA甲基化 癌症 基因 免疫疗法 生物 癌症研究 肿瘤科 DNA错配修复 医学 内科学 生物信息学 基因表达 遗传学 微卫星 等位基因
作者
Yuehan Yin,Shangjiu Yang,Zhijian Huang,Yang Zheng,Changhua Zhang,Yulong He
出处
期刊:Carcinogenesis [Oxford University Press]
卷期号:45 (5): 337-350 被引量:1
标识
DOI:10.1093/carcin/bgae004
摘要

Abstract The role of RNA methylation is vital in the advancement and spread of tumors. However, its exact role in microsatellite instability in colorectal cancer (CRC) is still not fully understood. To address this gap in knowledge, this study investigated the impact of genes associated with RNA methylation on the prognosis and response to immunotherapy in individuals diagnosed with low microsatellite instability (MSI-L) or microsatellite stable (MSS) CRC. The differentially expressed genes (DEGs) in two groups of patients: those with high microsatellite instability (MSI-H) and those with MSI-L/MSS was thoroughly investigated and compared with aims of exploring the association between them and the 60 RNA methylation regulators. We employed these genes and developed an MSI-RMscore to establish a risk signature capable of forecasting patient outcomes. Furthermore, an investigation of the immunophenotypic traits was conducted encompassing patients categorized as high-risk and low-risk. By combining the MSI-RMscore and clinicopathological features, a predictive nomogram was developed, which was subsequently validated using the GEO database. Furthermore, immunohistochemistry was employed to establish the correlation between INHBB and SOWAHA and the MSI status, as well as patient prognosis. Our findings indicated that the high-risk subgroup exhibited unfavorable overall survival rates, reduced responsiveness to immune checkpoint blockers, elevated estimate scores, and increased infiltration of macrophages and fibroblasts. We also confirmed that INHBB and SOWAHA were associated with CRC patient prognosis and MSI status, as well as immunotherapy response. These findings suggest that targeting INHBB and SOWAHA could be a promising strategy to enhance patient responsiveness to immunotherapy.
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