Identification of Radiotherapy-Associated Genes in Lung Adenocarcinoma by an Integrated Bioinformatics Analysis Approach.

ABSTRACT

Radiotherapy (RT) plays an important role in the prognosis of lung adenocarcinoma (LUAD) patients, but the radioresistance (RR) of LUAD is still a challenge that needs to be overcome. The current study aimed to investigate LUAD patients with RR to illuminate the underlying mechanisms. We utilized gene set variation analysis (GSVA) and The Cancer Immunome Atlas (TCIA) database to characterize the differences in biological functions and neoantigen-coding genes between RR and radiosensitive (RS) patients. Weighted Gene co-expression network analysis (WGCNA) was used to explore the relationship between RT-related traits and hub genes in two modules, i.e., RR and RS; two representative hub genes for RR (MZB1 and DERL3) and two for RS (IFI35 and PSMD3) were found to be related to different RT-related traits. Further analysis of the hub genes with the Lung Cancer Explorer (LCE), PanglaoDB and GSVA resources revealed the differences in gene expression levels, cell types and potential functions. On this basis, the Tumor and Immune System Interaction Database (TISIDB) was used to identify the potential association between RR genes and B cell infiltration. Finally, we used the Computational Analysis of Resistance (CARE) database to identify specific gene-associated drugs for RR patients and found that GSK525762A and nilotinib might be promising candidates for RR treatment. Taken together, these results demonstrate that B cells in TME may have a significant impact on the RT and that these two drug candidates, GSK525762A and nilotinib, might be helpful for the treatment of RR patients.