Integrative analyses identified ion channel genes GJB2 and SCNN1B as prognostic biomarkers and therapeutic targets for lung adenocarcinoma

Ao Lu; Yidan Shi; Yijuan Liu; Jiahao Lin; Huarong Zhang; Yating Guo; Lisheng Li; Zeman Lin; Junling Wu; Daihan Ji; Chengdang Wang

doi:10.1016/j.lungcan.2021.06.001

Integrative analyses identified ion channel genes GJB2 and SCNN1B as prognostic biomarkers and therapeutic targets for lung adenocarcinoma

Lung Cancer. 2021 Aug:158:29-39. doi: 10.1016/j.lungcan.2021.06.001. Epub 2021 Jun 6.

Authors

Ao Lu¹, Yidan Shi², Yijuan Liu³, Jiahao Lin², Huarong Zhang², Yating Guo², Lisheng Li⁴, Zeman Lin², Junling Wu², Daihan Ji², Chengdang Wang⁵

Affiliations

¹ Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350122, China; Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China. Electronic address: lukey@fjmu.edu.cn.
² Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, School of Medical Technology and Engineering, Fujian Medical University, Fuzhou, China.
³ Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350122, China.
⁴ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
⁵ Department of Gastroenterology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, 350122, China. Electronic address: wangcdhl@fjmu.edu.cn.

PMID: 34111567
DOI: 10.1016/j.lungcan.2021.06.001

Abstract

Objectives: Abnormal expressions of ion channel genes are associated with the occurrence and progression of tumors. At present, their roles in the carcinogenesis of lung adenocarcinoma (LUAD) are not clear.

Materials and methods: Differentially expressed (DE) genes in the tumorigenesis were identified from 328 ion channel genes in 102 LUAD and paired adjacent normal samples. Similar analyses were performed between 177 metastatic and 286 non-metastatic LUAD samples to identify DE ion channel genes in the progression of LUAD. Independent prognostic factors selected from DE ion channel genes were used to construct a prognostic model. Correlation analysis and drugs-drug targets interaction network were used to screen the potential drugs for LUAD patients stratified by GJB2 or SCNN1B.

Results: Six ion channel genes (GJB2, CACNA1D, KCNQ1, SCNN1B, SCNN1G and TRPV6) were continuous differentially expressed in the tumorigenesis and progression of LUAD. The survival analysis in four datasets with 522 LUAD samples showed that GJB2 and SCNN1B were independent prognostic biomarkers. Patients with overexpression of GJB2 or underexpression of SCNN1B had shorter overall survival. Moreover, multi-omics analysis showed that hypomethylation of GJB2 and hypermethylation of SCNN1B in the promoter region may contribute to their aberrant expressions. KEGG enrichment analysis showed that the overexpressed genes in the group with high GJB2 or low SCNN1B were enriched in cancer-related pathways, while the underexpressed genes were enriched in metabolism-related pathways. The prognostic model with GJB2 and SCNN1B can stratify all LUAD patients into two groups with significantly different survival. Correlation analysis and drugs-drug targets interaction network suggested that GJB2 and SCNN1B expression might have indicative therapeutic values for LUAD patients. Finally, pan-cancer analysis in other eight cancer types showed that GJB2 and SCNN1B might be also potential prognostic factors for KIRC.

Conclusions: GJB2 and SCNN1B were identified as prognostic biomarkers and therapeutic targets for LUAD.

Keywords: Gene expression; Ion channel genes; Lung adenocarcinoma; Multi-omics analysis; Prognostic model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung* / drug therapy
Adenocarcinoma of Lung* / genetics
Biomarkers, Tumor / genetics
Connexin 26 / genetics*
Epithelial Sodium Channels / genetics*
Gene Expression Regulation, Neoplastic
Humans
Ion Channels / genetics
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Prognosis

Substances

Biomarkers, Tumor
Epithelial Sodium Channels
GJB2 protein, human
Ion Channels
SCNN1B protein, human
Connexin 26