Identification and validation of novel prognostic biomarkers and therapeutic targets for non-small cell lung cancer

Li-Ting Lai; Yuan-Hui Ren; Ya-Jun Huai; Yu Liu; Ying Liu; Shan-Shan Wang; Jin-Hong Mei

doi:10.3389/fgene.2023.1139994

Identification and validation of novel prognostic biomarkers and therapeutic targets for non-small cell lung cancer

Front Genet. 2023 Mar 16:14:1139994. doi: 10.3389/fgene.2023.1139994. eCollection 2023.

Authors

Li-Ting Lai^{1

2}, Yuan-Hui Ren^{2

3}, Ya-Jun Huai^{1

2}, Yu Liu^{2

3}, Ying Liu^{2

3}, Shan-Shan Wang^{2

3}, Jin-Hong Mei^{2

3}

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
² Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
³ Institute of Molecular Pathology, Nanchang University, Nanchang, Jiangxi, China.

Abstract

Background: Despite the significant survival benefits of anti-PD-1/PD-L1 immunotherapy, non-small cell lung cancer (NSCLC) remains one of the most common tumors and major causes of cancer-related deaths worldwide. Thus, there is an urgent need to identify new therapeutic targets for this refractory disease. Methods: In this study, microarray datasets GSE27262, GSE75037, GSE102287, and GSE21933 were integrated by Venn diagram. We performed functional clustering and pathway enrichment analyses using R. Through the STRING database and Cytoscape, we conducted protein-protein interaction (PPI) network analysis and identified the key genes, which were verified by the GEPIA2 and UALCAN portal. Validation of actin-binding protein anillin (ANLN) was performed by quantitative real-time polymerase chain reaction and Western blotting. Additionally, Kaplan-Meier methods were used to compute the survival analyses. Results: In total, 126 differentially expressed genes were identified, which were enriched in mitotic nuclear division, mitotic cell cycle G2/M transition, vasculogenesis, spindle, and peroxisome proliferator-activated receptor signaling pathway. 12 central node genes were identified in the PPI network complex. The survival analysis revealed that high transcriptional levels were associated with inferior survival in NSCLC patients. The clinical implication of ANLN was further explored; its protein expression showed a gradually increasing trend from grade I to III. Conclusion: These Key genes may be involved in the carcinogenesis and progression of NSCLC, which may serve as useful targets for NSCLC diagnosis and treatment.

Keywords: biological process; differentially expressed genes; gene expression omnibus; non-small cell lung cancer; protein-protein interaction.

Grants and funding

This work was funded by the National Natural Science Foundation of China (No. 81560410); Science and Technology Project of Jiangxi Provincial Administration of Traditional Chinese Medicine (No. 2020B0365); Science and Technology Planning Project of Jiangxi Provincial Health Department (No. 20203122).