Identification and Validation of an Endoplasmic Reticulum Stress-Related lncRNA Signature for Colon Adenocarcinoma Patients

Abstract

Xueru Chen,1,* Kai Gao,2,* Zijin Xiang,1 Yujun Zhang,1 Xiangdong Peng1 1Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangdong Peng, Department of Pharmacy, The Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan Province, 410013, People’s Republic of China, Email [email protected]: Endoplasmic reticulum (ER) stress has a significant effect on cancer cells. Increasing numbers of studies indicate that long non-coding RNAs (lncRNAs) promote the development of colon adenocarcinoma (COAD), but the relationship between ER stress-related lncRNAs and the prognosis of COAD remains unclear. The aim of the current study was to construct and validate an ER stress-related lncRNA prognostic signature to predict COAD prognoses.Methods: Gene expression data and clinical information from the Cancer Genome Atlas and the Gene Expression Omnibus with COAD were downloaded and analyzed. Cox regression and least absolute shrinkage and selection operator regression were then used to develop an ER stress-related lncRNA signature. COAD patients were then divided into high-risk and low-risk groups based on the median risk score to analyze prognoses. Tumor mutation burdens (TMBs) and the differences in copy number variations (CNVs) between the two groups were also analyzed. Lastly, gene set enrichment analysis (GSEA) was used to explore the enrichment pathways and biological processes associated with differentially expressed genes in the high-risk and low-risk groups, and lncRNA expression in the model was validated via quantitative real-time PCR in colon cancer and paracancerous tissues.Results: A signature including 8 ER stress-related lncRNAs was constructed. COAD prognoses were significantly poorer in the high-risk group than in the low-risk group. There were few differences in TMBs and CNVs between the two groups. In GSEA analysis, in the high-risk group highly expressed genes associated with extracellular matrix pathways were significantly enriched.Conclusion: The 8-ER stress-related lncRNA derived from the present study is a potential indicator of COAD prognosis.Keywords: TCGA, GEO, colon adenocarcinoma, endoplasmic reticulum stress, long non-coding RNA

Keywords

• tcga
• geo
• colon adenocarcinoma
• endoplasmic reticulum stress
• long non-coding rna;