Original Article
Identification of potential biomarkers in lung adenocarcinoma brain metastases by bioinformatics analysis
Zhang Xiaoyue, Yang Wendi, Zheng Taihao, Peng Yuan, Yang Zhenzhou
Published 2020-09-30
Cite as Chin J Metastatic Cancer, 2020, 03(3): 205-210. DOI: 10.3760/cma.j.cn101548-20200630-00091
Abstract
ObjectiveTo identify hub genes related to lung adenocarcinoma brain metastasis by bioinformatics analysis, which would provide theoretical basis for the prevention and treatment of brain metastases from lung cancer.
MethodsThe gene expression profilings of the primary lung adenocarcinoma (GSE10072) and brain metastasis (GSE14108) were used by searching the CEO database. Differentially expressed genes (DEGs) were screened by R software and the GO function annotation and KEGG metabolic pathway analysis of DEGs were performed by clusterProfiler software package. The hub genes were obtained by protein-protein interaction (PPI) network analysis using STRING database combined with Cytoscape software. The influence of expression of identified hub genes on prognosis of lung cancer patients and tumor invasion and metastases were performed using TCGA database in UALCAN online analysis tool and GSEA analysis, respectively.
ResultsA total of 298 DEGs were selected, of which 51 genes were down-regulated and 248 genes were up-regulated. The results of GO function analysis and KEGG pathway analysis showed that these genes were mainly involved in extracellular matrix organization, humoral immune response, chemokine, and chemokine receptors and were mainly enriched in ubiquitin-mediated proteolysis and chemokine signaling pathways. PPI network construction identified 8 hub genes, among which KLHL5 was shown as novel potential biomarkers for predicting brain metastasis of lung adenocarcinoma. Moreover, the KLHL5 high expression groups showed enrichment in tumor invasion and metastasis-related pathways, and were associated with poor prognosis in patients with lung adenocarcinoma.
ConclusionThe biological role of extracellular matrix, chemokine signaling pathway and 8 key hub genes shown as potential therapeutic targets for inhibiting lung adenocarcinoma brain metastasis.
Key words:
Brain metastasis, liung neoplasms; Bioinformatics; Hub genes; Biomarker
Contributor Information
Zhang Xiaoyue
Cancer Center, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
Yang Wendi
Cancer Center, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
Zheng Taihao
Cancer Center, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
Peng Yuan
Cancer Center, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
Yang Zhenzhou
Cancer Center, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China