Cancer Management and Research (Sep 2022)

Identification of Key Genes and FUNCTIONAL Pathway in Radioresistance of Non-Small Cell Lung Cancer

  • Li S,
  • Feng J,
  • Weng H,
  • Zhao F,
  • Cui G,
  • Fu W,
  • Lin X,
  • Hu H

Journal volume & issue
Vol. Volume 14
pp. 2871 – 2884

Abstract

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Shouying Li,1,* Jiaxin Feng,2,* Haiyan Weng,1 Feng Zhao,3 Guohui Cui,1 Wenkui Fu,1 Xiaorong Lin,4 Hai Hu1,5 1Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Research and Development Department, Guangzhou BioBlue Technology Co. Ltd, Guangzhou, People’s Republic of China; 4Diagnosis and Treatment Center of Breast Diseases, Shantou Central Hospital, Shantou, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaorong Lin; Hai Hu, Email [email protected]; [email protected]: For better understanding of radiotherapy resistance and its potential mechanism.Methods: We established radioresistance cell lines of non-small cell lung cancer (NSCLC) followed by microarray analysis. 529 differentially expressed genes (DEGs) were then screened between radiation resistant cell lines compared with the sensitive cell lines. The biological functions and enrichment pathways of the above DEGs were identified using Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses. Gene Set Enrichment Analysis (GSEA) revealed that the radiation resistance group had the most gene sets enriched in altered immune response, such as TNF signaling pathway, when compared to the radiation sensitive group. Protein-protein interaction (PPI) network was carried out through the STRING database, and then five hub genes (CXCL10, IFIH1, DDX58, CXCL11, RSAD2) were screened by Cytoscape software. RT-PCR confirmed the expression of the above hub genes. ChIP-X Enrichment Analysis showed that STAT1 might be the transcription factor of the above hub genes. Considering that PD-L1 could be activated by STAT1 in a variety of tumors and ultimately lead to immune exhaustion, RT-PCR and Western blot verified the expression level of PD-L1.Results: Five hub genes (CXCL10, IFIH1, DDX58, CXCL11, RSAD2) were screened and verified to be highly expressed in radioresistance group, STAT1 might be the transcription factor of the above hub genes. Our study found that the expression level of PD-L1 was increased after radiotherapy resistance.Conclusion: Although immune system activation occurs followed by radiation resistance, we hypothesized that the upregulation of PD-L1 expression caused by STAT1 activation might be one of the mechanisms of radiotherapy resistance.Keywords: NSCLC, radioresistance, DEGs, hub gene, STAT1

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