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MAGE-A3 通过 PI3K/AKT 通路调节胃癌中的肿瘤干性。

MAGE-A3 regulates tumor stemness in gastric cancer through the PI3K/AKT pathway.

机构信息

Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei 430081, China.

Yueyang Vocational and Technical College, Yueyang Key Laboratory of Chronic Noncommunicable Diseases, Yueyang 414000, Hunan, China.

出版信息

Aging (Albany NY). 2022 Nov 8;14(23):9579-9598. doi: 10.18632/aging.204373.

Abstract

Gastric cancer remains a malignant disease of the digestive tract with high mortality and morbidity worldwide. However, due to its complex pathological mechanisms and lack of effective clinical therapies, the survival rate of patients after receiving treatment is not satisfactory. A increasing number of studies have focused on cancer stem cells and their regulatory properties. In this study, we first constructed a co-expression network based on the WGCNA algorithm to identify modules with different degrees of association with tumor stemness indices. After selecting the most positively correlated modules of the stemness index, we performed a consensus clustering analysis on gastric cancer samples and constructed the co-expression network again. We then selected the modules of interest and applied univariate COX regression analysis to the genes in this module for preliminary screening. The results of the screening were then used in LASSO regression analysis to construct a risk prognostic model and subsequently a sixteen-gene model was obtained. Finally, after verifying the accuracy of the module and screening for risk genes, we identified MAGE-A3 as the final study subject. We then performed and experiments to verify its effect on tumor stemness and tumour proliferation. Our data supports that MAGE-A3 is a tumor stemness regulator and a potent prognostic biomarker which can help the prediction and treatment of gastric cancer patients.

摘要

胃癌仍然是一种具有高死亡率和发病率的恶性消化道疾病。然而,由于其复杂的病理机制和缺乏有效的临床治疗方法,接受治疗后的患者的存活率并不令人满意。越来越多的研究集中在癌症干细胞及其调节特性上。在这项研究中,我们首先基于 WGCNA 算法构建了一个共表达网络,以识别与肿瘤干性指数具有不同程度关联的模块。在选择与干性指数最正相关的模块后,我们对胃癌样本进行了共识聚类分析,并再次构建了共表达网络。然后,我们选择了感兴趣的模块,并对该模块中的基因进行单变量 COX 回归分析进行初步筛选。筛选结果随后用于 LASSO 回归分析,以构建风险预后模型,随后获得了一个 16 基因模型。最后,在验证模块的准确性和筛选风险基因后,我们确定 MAGE-A3 为最终研究对象。我们进行了 和 实验来验证其对肿瘤干性和肿瘤增殖的影响。我们的数据支持 MAGE-A3 是一种肿瘤干性调节剂和强有力的预后生物标志物,可以帮助预测和治疗胃癌患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49b0/9792200/f284ffa7f1b3/aging-14-204373-g001.jpg

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