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基于自噬相关长链非编码 RNA 分析的结肠腺癌预后指标的建立。

Development of Prognostic Indicator Based on Autophagy-Related lncRNA Analysis in Colon Adenocarcinoma.

机构信息

School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Biomed Res Int. 2020 Sep 2;2020:9807918. doi: 10.1155/2020/9807918. eCollection 2020.

Abstract

There were no systematic researches about autophagy-related long noncoding RNA (lncRNA) signatures to predict the survival of patients with colon adenocarcinoma. It was necessary to set up corresponding autophagy-related lncRNA signatures. The expression profiles of lncRNAs which contained 480 colon adenocarcinoma samples were obtained from The Cancer Genome Atlas (TCGA) database. The coexpression network of lncRNAs and autophagy-related genes was utilized to select autophagy-related lncRNAs. The lncRNAs were further screened using univariate Cox regression. In addition, Lasso regression and multivariate Cox regression were used to develop an autophagy-related lncRNA signature. A risk score based on the signature was established, and Cox regression was used to test whether it was an independent prognostic factor. The functional enrichment of autophagy-related lncRNAs was visualized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Ten prognostic autophagy-related lncRNAs (AC027307.2, AC068580.3, AL138756.1, CD27-AS1, EIF3J-DT, LINC01011, LINC01063, LINC02381, AC073896.3, and SNHG16) were identified to be significantly different, which made up an autophagy-related lncRNA signature. The signature divided patients with colon adenocarcinoma into the low-risk group and the high-risk group. A risk score based on the signature was a significantly independent factor for the patients with colon adenocarcinoma (HR = 1.088, 95%CI = 1.057 - 1.120; < 0.001). Additionally, the ten lncRNAs were significantly enriched in autophagy process, metabolism, and tumor classical pathways. In conclusion, the ten autophagy-related lncRNAs and their signature might be molecular biomarkers and therapeutic targets for the patients with colon adenocarcinoma.

摘要

目前尚无系统的研究探讨自噬相关长链非编码 RNA(lncRNA)标志物以预测结肠腺癌患者的生存情况。因此,有必要建立相应的自噬相关 lncRNA 标志物。本研究从癌症基因组图谱(TCGA)数据库中获取了包含 480 例结肠腺癌样本的 lncRNA 表达谱。利用 lncRNA 与自噬相关基因的共表达网络筛选出自噬相关 lncRNA。进一步采用单变量 Cox 回归筛选 lncRNA。此外,采用 Lasso 回归和多变量 Cox 回归建立自噬相关 lncRNA 标志物。根据该标志物建立风险评分,并采用 Cox 回归检验其是否为独立预后因素。采用基因本体论和京都基因与基因组百科全书可视化自噬相关 lncRNA 的功能富集。确定了 10 个与预后相关的自噬相关 lncRNA(AC027307.2、AC068580.3、AL138756.1、CD27-AS1、EIF3J-DT、LINC01011、LINC01063、LINC02381、AC073896.3 和 SNHG16),它们的差异具有统计学意义,这些 lncRNA 组成了一个自噬相关 lncRNA 标志物。该标志物将结肠腺癌患者分为低风险组和高风险组。基于该标志物的风险评分是结肠腺癌患者的显著独立预后因素(HR=1.088,95%CI=1.057-1.120;<0.001)。此外,这 10 个 lncRNA 显著富集于自噬过程、代谢和肿瘤经典途径。综上所述,这 10 个自噬相关 lncRNA 及其标志物可能是结肠腺癌患者的分子生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e2/7486634/e6bb285a68d5/BMRI2020-9807918.001.jpg

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