PeerJ | 卷:9 |
Homologous recombination repair rathway and RAD54L in early-stage lung adenocarcinoma | |
Michael Lanuti1  Shaopeng Zheng2  Haiyu Zhou3  Luyu Huang3  Lintong Yao3  Fasheng Li3  Jin Xia3  Hao Li4  Zenan Lin4  Yunfang Yu5  | |
[1] Department of Surgery, Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA, USA; | |
[2] Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, P.R. China; | |
[3] Division of Thoracic Surgery, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, P.R. China; | |
[4] Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China; | |
[5] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Phase I Clinical Trial Centre, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China; | |
关键词: Lung adenocarcinoma; Homologous recombination repair; RAD54L; Prognostic factor; | |
DOI : 10.7717/peerj.10680 | |
来源: DOAJ |
【 摘 要 】
Objective The current study aims to identify the dysregulated pathway involved in carcinogenesis and the essential survival-related dysregulated genes among this pathway in the early stage of lung adenocarcinoma (LUAD). Patients and Methods Data from The Cancer Genome Atlas (TCGA) including 526 tumor tissues of LUAD and 59 healthy lung tissues were analyzed to gain differentially expressed genes (DEGs). Gene ontology (GO) analysis was conducted with DAVID, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs was performed, followed by gene set enrichment analysis (GSEA) methods. Survival analysis was implemented in TCGA dataset and validated in Gene Expression Omnibus (GEO) cohort GSE50081, which includes 127 patients with stage I LUAD. Results GSEA enrichment analysis suggested that homologous recombination repair (HRR) pathway was significantly enriched. Subsequent KEGG pathway enrichment analysis indicated the significant up-regulation of HRR pathway in patients with T1 stage LUAD. Retrieved in Gene database, RAD54L is involved in HRR pathway and were recognized to be significantly differentially expressed in T1 stage LUAD in our study. The survival analysis indicated that high expression of RAD54L was significantly related to worse overall survival in patients with T1 stage LUAD (TCGA cohort: HR=2.10, 95% CI [1.47–2.98], P = 0.001; GSE50081 validation cohort: HR = 2.61, 95% CI [1.51–4.52], P = 0.002). Multivariate cox regression analysis indicated that RAD54L is an independent prognostic factor in the early-stage LUAD. Conclusion HRR pathway is up-regulated in LUAD, among which the expression of RAD54L was found to be significantly differentially expressed in T1 stage tumor tissue. Patients with high expression of RAD54L were associated with worse overall survival in the TCGA cohort and validation cohort. This study suggests a potential mechanism of lung cancer progression and provide a budding prognostic factor and treatment target in early-stage LUAD.
【 授权许可】
Unknown