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.

IF 3.3 3区 医学 Q2 ONCOLOGY
Yuehan Yin, Shangjiu Yang, Zhijian Huang, Zheng Yang, Changhua Zhang, Yulong He
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引用次数: 0

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.

RNA 甲基化相关基因 INHBB 和 SOWAHA 与结直肠癌患者的 MSI 状态相关,可作为预测免疫疗法疗效的预后标志物。
RNA 甲基化对肿瘤的发展和扩散至关重要。然而,人们对其在结直肠癌(CRC)微卫星不稳定性中的确切作用仍不完全了解。为了填补这一知识空白,本研究调查了与RNA甲基化相关的基因对低微卫星不稳定性(MSI-L)或微卫星稳定型(MSS)CRC患者的预后和免疫疗法反应的影响。我们对两组患者:高微卫星不稳定性(MSI-H)患者和 MSI-L/MSS 患者的差异表达基因(DEGs)进行了深入研究和比较,旨在探索它们与 60 个 RNA 甲基化调节因子之间的关联。我们利用这些基因并开发了 MSI-RMscore 来建立能够预测患者预后的风险特征。此外,我们还对高风险和低风险患者的免疫表型特征进行了调查。通过结合 MSI-RMscore 和临床病理特征,得出了一个预测性提名图,随后利用 GEO 数据库对其进行了验证。此外,我们还利用免疫组化技术建立了INHBB和SOWAHA与MSI状态以及患者预后之间的相关性。我们的研究结果表明,高风险亚组的总生存率较差,对免疫检查点阻断剂的反应性降低,估计评分升高,巨噬细胞和成纤维细胞浸润增加。我们还证实,INHBB和SOWAHA与CRC患者的预后、MSI状态以及免疫治疗反应有关。这些研究结果表明,以 INHBB 和 SOWAHA 为靶点可能是提高患者对免疫疗法反应性的一种有前途的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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