Prognostic Impact of the Angiogenic Gene POSTN and Its Related Genes on Lung Adenocarcinoma

Dongfeng Sun; Zhibo Gai; Jie Wu; Qingfa Chen

doi:10.3389/fonc.2022.699824

Prognostic Impact of the Angiogenic Gene POSTN and Its Related Genes on Lung Adenocarcinoma

Front Oncol. 2022 Jun 27:12:699824. doi: 10.3389/fonc.2022.699824. eCollection 2022.

Authors

Dongfeng Sun¹, Zhibo Gai², Jie Wu³, Qingfa Chen⁴

Affiliations

¹ Department of Thoracic Surgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Emergency Medicine, Shandong Lung Cancer Institute, Shandong Institute of Respiratory Diseases, Jinan, China.
² Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
³ Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.
⁴ Institute of Tissue Engineering and Regenerative Medicine, Liaocheng People's Hospital, Liaocheng, China.

Abstract

Background: The function of angiogenesis-related genes (ARGs) in lung adenocarcinoma (LUAD) remains poorly documented. This study was designed to reveal ARGs in LUAD and related networks.

Methods: We worked with sequencing data and clinical information pertaining to LUAD from public databases. ARGs were retrieved from the HALLMARK_ANGIOGENESIS gene set. Differential analysis and Kaplan-Meier (K-M) analysis were performed to authenticate the ARGs associated with LUAD. Weighted gene correlation network analysis was performed on the mining hub genes linked to the abovementioned genes, and functional enrichment analysis was done. Subsequently, Cox regression analyses were used to construct the prognostic gene. POSTN and microvessel density were detected using immunohistochemistry.

Results: POSTN, an ARG that was highly expressed in patients with LUAD and was closely associated with their weak overall survival was identified. Differentially expressed genes associated with POSTN were mainly enriched in entries related to the tubulointerstitial system, immune response, and epithelial cells. A positive correlation was demonstrated between POSTN expression and tumor microvessel density in LUAD. Subsequently, a prognostic gene signature was constructed and revealed that 4 genes may predict the survival of LUAD patients. Furthermore, the ESTIMATE and CIBERSORT analyses suggested that our risk scoring system may be implicated in altering the immune microenvironment of patients with LUAD. Finally, a ceRNA network was constructed based on the prognostic genes, and the regulatory networks were examined.

Conclusion: POSTN, a novel prognostic gene signature associated with ARGs, was constructed for the prognosis of patients with LUAD. This signature may alter the immune microenvironment by modulating the activation of the tubulointerstitial system, epithelial cells, and immune cells, ultimately affecting patient survival.

Keywords: angiogenesis; angiogenesis-related genes; competing endogenous RNA; lung adenocarcinoma; prognosis.