AUTHOR=Xie Yuning , Wu Hongjiao , Hu Wenqian , Zhang Hongmei , Li Ang , Zhang Zhi , Ren Shuhua , Zhang Xuemei 

TITLE=Identification of Hub Genes of Lung Adenocarcinoma Based on Weighted Gene Co-Expression Network in Chinese Population

JOURNAL=Pathology and Oncology Research

VOLUME=28

YEAR=2022

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610455

DOI=10.3389/pore.2022.1610455

ISSN=1532-2807

ABSTRACT=<p><bold>Purpose:</bold> Lung adenocarcinoma is one of the most common malignancies. Though some historic breakthroughs have been made in lung adenocarcinoma, its molecular mechanisms of development remain elusive. The aim of this study was to identify the potential genes associated with the lung adenocarcinoma progression and to provide new ideas for the prognosis evaluation of lung adenocarcinoma.</p><p><bold>Methods:</bold> The transcriptional profiles of ten pairs of snap-frozen tumor and adjacent normal lung tissues were obtained by performing RNA-seq. Weighted gene co-expression network analysis (WGCNA) was used to construct free-scale gene co-expression networks in order to explore the associations of gene sets with the clinical features and to investigate the functional enrichment analysis of co-expression genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Set Enrichment Analysis (GSEA) analyses were performed using clusterProfiler. The protein-protein network (PPI) was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and hub genes were identified using Cytohubba in Cytoscape. Transcription factor enrichment analysis was performed by the RcisTarget program in R language.</p><p><bold>Results:</bold> Based on RNA-seq data, 1,545 differentially expressed genes (DEGs) were found. Eight co-expression modules were identified among these DEGs. The blue module exhibited a strong correlation with LUAD, in which <italic>ADCY4</italic>, <italic>RXFP1</italic>, <italic>AVPR2</italic>, <italic>CALCRL</italic>, <italic>ADRB1</italic>, <italic>RAMP3</italic>, <italic>RAMP2</italic> and <italic>VIPR1</italic> were hub genes. A low expression level of <italic>RXFP1</italic>, <italic>AVPR</italic>2, <italic>ADRB1</italic> and <italic>VIPR1</italic> was detrimental to the survival of LUAD patients. Genes in the blue module enriched in 86 Gene Ontology terms and five KEGG pathways. We also found that transcription factors <italic>EGR3</italic> and <italic>EXOSC3</italic> were related to the biological function of the blue module. Overall, this study brings a new perspective to the understanding of LUAD and provides possible molecular biomarkers for prognosis evaluation of LUAD.</p>