Identification of prognostic indicator based on hypoxia-related lncRNAs analysis in lung adenocarcinoma

Jiaojiao Zhang 1, Blessed Kondowe 2, Hui Zhang 3, Xinming Xie 4, Qiang Song 5, Bo Guo 6* and Jin Shang 3*

1 Department of Pathology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China

2 Radiology Department, Mzuzu Central Hospital, Mzuzu, Malawi

3 Department of Medical Imaging, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China

4 Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China

5 Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China

6 Institute of Genetics and Developmental Biology, Translational Medicine Institute, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, P.R. China

Bo Guo and Jin Shang contributed equally to this work

*Corresponding Author:

Bo guo; E-mail: bo_guo@xjtu.edu.cn

Jin shang; E-mail: shangjin01@qq.com

Abstract

Introduction: There were no systematic studies about hypoxia-related long noncoding RNAs (lncRNAs) signatures to predict the survival of patients with lung adenocarcinoma (LUAD). Setting up matching hypoxia-related lncRNA signatures was necessary.

Objective: This study aimed to establish hypoxia-related lncRNAs signatures and to seek new biomarkers to predict the prognosis of the patients with lung adenocarcinoma.

Methodology: The Cancer Genome Atlas (TCGA) database provided the expression profiles of lncRNAs that includes 535 lung adenocarcinoma samples. The coexpression network of lncRNAs and hypoxia-related different expression genes (DEGs) was utilized to select hypoxia-related lncRNAs. The lncRNAs were further screened using univariate Cox regression. In addition, Lasso regression and multivariate Cox regression were used to develop a hypoxia-related lncRNAs signature. A risk score based on the signature was established, and Cox regression was used to test if it was an independent prognostic factor.

Results: Nine prognostic hypoxia-related lncRNAs (LINC01150, AC010980.2, AL606489.1, AL034397.3, LINC00460, LINC02081, FAM83A-AS1, AL365181.2, and AC026355.1) were identified to be significantly different, which made up a hypoxia-related lncRNAs signature. The high-risk group had shorter OS compared with the low-risk group (P = 3.329e − 09, log-rank test). A risk score based on the signature was a significantly independent factor for the patients with LUAD (HR = 1.449, 95% CI = 1.312 − 1.602, P < 0.001).

Conclusion: The nine hypoxia-related lncRNAs and their signature might be molecular biomarkers and therapeutic targets for the patients with LUAD.

Key words: Hypoxia-related long noncoding RNAs; prognostic; lung adenocarcinoma

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