Chen Shuran, Dong Rui, Li Yan, Zheng Ni, Peng Guisen, Lu Fei, Qiu Quanwei, Wen Hexin, Wang Yitong, Wu Huazhang, Liu Mulin
Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Department of Gynecologic Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Front Genet. 2022 Jun 9;13:918159. doi: 10.3389/fgene.2022.918159. eCollection 2022.
mG is a post-transcriptional modification modality, however, limited research has been conducted on its role in colon cancer. DNA damage repair (DDR) is an important factor that contributes to colon cancer development, growth and chemoresistance. This study aimed to explore whether mG-related DNA damage repair genes may be used as biomarkers to predict the prognosis of colon cancer patients. We use non-negative matrix factorization (NMF) to type CRC patients into. Risk models were constructed using different expression genes in two clusters. We assessed the reliability of risk models with DCA curves, and a Nomogram. Meanwhile, The receiver operating characteristic and C-index curves were used to compare the predictive significance of the constructed risk models with other studies. In additional, we examined the significance of risk models on patients' immunity microenvironment and response to immune therapy. Finally, we used a series of cellular experiments to validate the effect of model genes on the malignant progression of CRC cells. Twenty-eight mG genes were obtained from the GSEA database. Multivariate Cox and LASSO Cox regression analysis was performed and eleven mG-related DDR genes were identified for constructing the risk model. Survival and stage of CRC patients were worser in the high-risk group than in the low-risk group for both the training and test sets. Additionally, the different immune microenvironment status of patients in the high- and low-risk groups, suggesting that patients in the low-risk group may be more sensitive to immunotherapy, particularly immune checkpoint inhibitors. Finally, we found that depletion of ATP2A1, one of the risk genes in our model, influence the biologic behaviour of CRC cells significantly. The mG-related DDR genes can be used as important markers for predicting patient prognosis and immunotherapy response. Our data suggest that ATP2A1 may promote the proliferation of colon cancer cells. These findings may provide new therapeutic targets for the treatment of colon cancer.
mG是一种转录后修饰方式，然而，关于其在结肠癌中的作用的研究有限。DNA损伤修复（DDR）是促成结肠癌发生、发展和化疗耐药的一个重要因素。本研究旨在探讨与mG相关的DNA损伤修复基因是否可作为预测结肠癌患者预后的生物标志物。我们使用非负矩阵分解（NMF）对结直肠癌患者进行分型。利用两个簇中的不同表达基因构建风险模型。我们用决策曲线分析（DCA）曲线和列线图评估风险模型的可靠性。同时，使用受试者工作特征曲线和C指数曲线来比较所构建的风险模型与其他研究的预测意义。此外，我们研究了风险模型对患者免疫微环境和免疫治疗反应的意义。最后，我们进行了一系列细胞实验来验证模型基因对结直肠癌细胞恶性进展的影响。从基因集富集分析（GSEA）数据库中获得了28个mG基因。进行了多变量Cox和LASSO Cox回归分析，并鉴定出11个与mG相关的DDR基因用于构建风险模型。在训练集和测试集中，高危组结直肠癌患者的生存率和分期均比低危组更差。此外，高危组和低危组患者的免疫微环境状态不同，这表明低危组患者可能对免疫治疗更敏感，尤其是免疫检查点抑制剂。最后，我们发现我们模型中的风险基因之一ATP2A1的缺失显著影响结直肠癌细胞的生物学行为。与mG相关的DDR基因可作为预测患者预后和免疫治疗反应的重要标志物。我们的数据表明ATP2A1可能促进结肠癌细胞的增殖。这些发现可能为结肠癌的治疗提供新的治疗靶点。
