Chen Guangyu, Yang Gang, Long Junyu, Yang Jinshou, Qin Cheng, Luo Wenhao, Qiu Jiangdong, Zhao Fangyu, You Lei, Zhang Taiping, Zhao Yupei
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Oncol. 2021 May 26;11:596573. doi: 10.3389/fonc.2021.596573. eCollection 2021.
Pancreatic cancer (PC) is a highly malignant tumor in the digestive system. Both long noncoding RNAs (lncRNAs) and autophagy play vital roles in the development and progress of PC. Here, we constructed a prognostic risk score system based on the expression profile of autophagy-associated lncRNAs for prognostic prediction in PC patients. Firstly, we extracted the expression profile of lncRNA and clinical information from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The autophagy-associated genes were from The Human Autophagy Database. Through Cox regression and survival analysis, we screened out seven autophagy-associated lncRNAs and built the risk score system in which the patients with PC were distinguished into high- and low-risk groups in both training and validation datasets. PCA plot displayed distinct discrimination, and risk score system displayed independently predictive value for PC patient survival time by multivariate Cox regression. Then, we built a lncRNA and mRNA co-expression network Cytoscape and Sankey diagram. Finally, we analyzed the function of lncRNAs in high- and low-risk groups by gene set enrichment analysis (GSEA). The results showed that autophagy and metabolism might make significant effects on PC patients of low-risk groups. Taken together, our study provides a new insight to understand the role of autophagy-associated lncRNAs and finds novel therapeutic and prognostic targets in PC.
胰腺癌(PC)是消化系统中一种高度恶性的肿瘤。长链非编码RNA(lncRNAs)和自噬在PC的发生发展过程中都起着至关重要的作用。在此,我们基于自噬相关lncRNAs的表达谱构建了一个预后风险评分系统,用于预测PC患者的预后。首先,我们从癌症基因组图谱(TCGA)和国际癌症基因组联盟(ICGC)数据库中提取lncRNA的表达谱和临床信息。自噬相关基因来自人类自噬数据库。通过Cox回归和生存分析,我们筛选出7个自噬相关lncRNAs,并构建了风险评分系统,在训练和验证数据集中将PC患者分为高风险组和低风险组。主成分分析(PCA)图显示出明显的区分度,风险评分系统通过多变量Cox回归对PC患者的生存时间显示出独立的预测价值。然后,我们利用Cytoscape和桑基图构建了lncRNA和mRNA共表达网络。最后,我们通过基因集富集分析(GSEA)分析了lncRNAs在高风险组和低风险组中的功能。结果表明,自噬和代谢可能对低风险组的PC患者产生显著影响。综上所述,我们的研究为理解自噬相关lncRNAs的作用提供了新的见解,并在PC中发现了新的治疗和预后靶点。