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Identifying autophagy gene-associated module biomarkers through construction and analysis of an autophagy-mediated ceRNA-ceRNA interaction network in colorectal cancer

机译:通过构建和分析自噬介导的ceRNA-ceRNA相互作用网络在结直肠癌中鉴定自噬基因相关的模块生物标志物

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摘要

Autophagy is crucial in cellular homeostasis and has been implicated in the development of malignant tumors. However, the regulatory function of autophagy in cancer remains to be fully elucidated. In the present study, the autophagy-mediated competing endogenous RNA (ceRNA)-ceRNA interaction networks in colorectal cancer (CRC) were constructed by integrating systematically expression profiles of long non-coding RNAs and mRNAs. It was found that a large proportion of autophagy genes were inclined to target hub nodes, including a fraction of autophagy genes, by comparing with other genes within ceRNA networks, and showed preferential interaction with themselves. The present study also revealed that autophagy genes may be used as prognostic markers for cancer therapy. A risk score model based on multivariable Cox regression analysis was then used to capture novel biomarkers in connection with lncRNA for the prognosis of CRC. These biomarkers were confirmed in the test dataset and an additional independent dataset. Furthermore, the prognostic value of biomarkers is independent of conventional clinical factors. These results provide improved understanding of autophagy-mediated ceRNA regulatory mechanisms in CRC and provide novel potential molecular therapeutic targets for the diagnosis and treatment of CRC.
机译:自噬在细胞动态平衡中至关重要,并已与恶性肿瘤的发展有关。然而,自噬在癌症中的调节功能仍有待充分阐明。在本研究中,通过整合长的非编码RNA和mRNA的系统表达谱,构建了大肠癌(CRC)中自噬介导的竞争性内源RNA(ceRNA)-ceRNA相互作用网络。通过与ceRNA网络中的其他基因进行比较,发现大部分自噬基因倾向于靶向集线器节点,包括一小部分自噬基因,并显示出与自身的优先相互作用。本研究还揭示了自噬基因可用作癌症治疗的预后标志物。然后使用基于多变量Cox回归分析的风险评分模型来捕获与lncRNA相关的新型生物标志物,以用于CRC的预后。这些生物标记已在测试数据集和其他独立数据集中得到确认。此外,生物标志物的预后价值与常规临床因素无关。这些结果提供了对CRC中自噬介导的ceRNA调控机制的更好理解,并为CRC的诊断和治疗提供了新的潜在分子治疗靶标。

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