Oncogenic Activation of the HRR Pathway Drives RAD54L Expression in Early Stage Lung Adenocarcinoma

Background: The current study aims to identify the key dysregulated genes and its related pathways in early progression of lung adenocarcinoma (LUAD). Methods: TCGA dataset of LUAD including 59 healthy lung tissues and 517 tumor tissues were utilized to detect differentially expressed mRNAs and lncRNAs. Gene ontology (GO) analysis was conducted with DAVID, while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes was performed using gene set enrichment analysis (GSEA) methods. Findings: 41 lncRNAs and 2,047 mRNAs were screened out as they were differentially expressed in LUAD. Besides, 38 lncRNAs and 1,801 mRNAs were found to be differentially expressed in T1 stage LUAD used 8th edition IASLC staging. The homologous recombination repair (HRR) pathway was found to be significantly up-regulated in LUAD, with four genes in this pathway up-regulated. In these genes of HRR pathway, PPP4R4 and RAD54L were recognized to be significantly differentially expressed in T1 stage, compared with T2 stage and T3 stage, which were putative biomarkers of early stage lung adenocarcinoma. The survival analysis revealed that expression of RAD54L was significantly related to survival rate (HR 1.54, 95% CI, 1.16-2.06; p=0.003) in patients with T1 stage tumor. Interpretation: HRR pathway was up-regulated in LUAD, in which the expression of PPP4R4 and RAD54L were found to be tumor stage-specific. RAD54L was associated with worse overall survival rate of T1 stage patients. This study suggests a potential mechanism of lung cancer progression in T1 stage patients. Funding Statement: The study was supported by Medical Scientific Research Foundation of Guangdong Province, China (Grant number B2018148), Science and Technology Program of Guangzhou, China (Grant number 201903010028), Natural Science Foundation of Guangdong Province, China (Grant number 2018A0303130113) and Guangdong Medical University College Students Innovation Experiment Project, China (Grant number ZZZF001). Declaration of Interests: All authors report no conflicts of interest.