Identification of potential prognostic markers for lung adenocarcinoma using comprehensive analysis

Liang Huang; Anqi Zhang; Chunyan Tang; Jinmei Wei; Miao Li; Shishan Yuan; Huihui Zhang; Xia Zhang

doi:10.3892/mmr.2023.13036

Identification of potential prognostic markers for lung adenocarcinoma using comprehensive analysis

Mol Med Rep. 2023 Aug;28(2):149. doi: 10.3892/mmr.2023.13036. Epub 2023 Jun 23.

Authors

Liang Huang¹, Anqi Zhang¹, Chunyan Tang², Jinmei Wei³, Miao Li³, Shishan Yuan¹, Huihui Zhang¹, Xia Zhang¹

Affiliations

¹ Department of Laboratory Medicine, Hunan Normal University School of Medicine, Changsha, Hunan 410013, P.R. China.
² Department of Laboratory Diagnosis, Changsha Kingmed Center for Clinical Laboratory, Changsha, Hunan 410221, P.R. China.
³ Department of Laboratory Diagnosis, Guangxi Kingmed Diagnostics Group Co., Ltd., Nanning, Guangxi 530009, P.R. China.

Abstract

Lung adenocarcinoma (LUAD) is a common malignancy throughout the world with high levels of mortality and morbidity. In the present study, potential biomarkers and treatment targets for LUAD were investigated using data from The Cancer Genome Atlas. Overall, 4,485 differentially expressed genes (DEGs) were identified (1,857 upregulated and 2,628 downregulated) between tumor and adjacent control tissues. Functional analysis with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Variation Analysis and Gene Set Enrichment Analysis revealed significant enrichment of the DEGs in pathways related to system development, cell cycle and cell adhesion. Weighted gene co‑expression network analysis distinguished ten co‑expression modules on inclusion of the clinical profiles of patients with LUAD. Of these, the blue/turquoise modules showed peak association with tumor onset. Analysis of hub modules identified five hub genes, namely ANGPTL7, SLC6A4, PTPRQ, KCNA4 and TEDC2 (also known as C16orf59). Survival analysis revealed associations between hub‑gene expression profiles and patient prognosis. Downregulation of SLC6A4 in LUAD tumor tissues was confirmed using immunohistochemistry. Additional assays (Cell Counting Kit‑8, colony formation, scratch assay, cell cycle, Transwell invasion assay and cell adhesion assay) revealed that SLC6A4 overexpression inhibited A549 cell growth, invasion and migration. The findings demonstrated that the hub genes could act as treatment targets or new biomarkers for LUAD.

Keywords: Hub genes; bioinformatics analysis; biomarkers; lung adenocarcinoma; weighted gene co‑expression network analysis.

MeSH terms

Adenocarcinoma of Lung* / pathology
Angiopoietin-Like Protein 7
Angiopoietin-like Proteins / genetics
Biomarkers, Tumor / genetics
Gene Expression Profiling
Humans
Lung Neoplasms* / diagnosis
Lung Neoplasms* / genetics
Prognosis
Receptor-Like Protein Tyrosine Phosphatases, Class 3 / genetics
Serotonin Plasma Membrane Transport Proteins / genetics

Substances

Biomarkers, Tumor
SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins
PTPRQ protein, human
Receptor-Like Protein Tyrosine Phosphatases, Class 3
ANGPTL7 protein, human
Angiopoietin-like Proteins
Angiopoietin-Like Protein 7

Grants and funding

The present study was supported by grants from the National Natural Science Foundation of China (NSFC) (grant no. 81602450), the Natural Science Foundation of Hunan Province, China (grant no. 2018JJ3337), the Hunan Provincial Health Commission Project (grant no. 202202084830), the Key Project of Developmental Biology and Breeding from Hunan Province (grant no. 2022XKQ0205), and the Key Project of Education Department of Hunan Province (grant no.20A308).