Shaopeng Zheng1,2, Lintong Yao3,2, Fasheng Li3,4, Luyu Huang3,2, Yunfang Yu5, Zenan Lin6, Hao Li6, Jin Xia3, Michael Lanuti7, Haiyu Zhou3,2. 1. Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, P.R. China. 2. Shantou University Medical College, Shantou, 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. The Second School of Clinical Medicine, Southern Medical University, 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. 6. Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China. 7. Department of Surgery, Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA, USA.
Abstract
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.
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.
Authors: J Essers; R W Hendriks; S M Swagemakers; C Troelstra; J de Wit; D Bootsma; J H Hoeijmakers; R Kanaar Journal: Cell Date: 1997-04-18 Impact factor: 41.582
Authors: Mariam Jamal-Hanjani; Gareth A Wilson; Nicholas McGranahan; Nicolai J Birkbak; Thomas B K Watkins; Selvaraju Veeriah; Seema Shafi; Diana H Johnson; Richard Mitter; Rachel Rosenthal; Max Salm; Stuart Horswell; Mickael Escudero; Nik Matthews; Andrew Rowan; Tim Chambers; David A Moore; Samra Turajlic; Hang Xu; Siow-Ming Lee; Martin D Forster; Tanya Ahmad; Crispin T Hiley; Christopher Abbosh; Mary Falzon; Elaine Borg; Teresa Marafioti; David Lawrence; Martin Hayward; Shyam Kolvekar; Nikolaos Panagiotopoulos; Sam M Janes; Ricky Thakrar; Asia Ahmed; Fiona Blackhall; Yvonne Summers; Rajesh Shah; Leena Joseph; Anne M Quinn; Phil A Crosbie; Babu Naidu; Gary Middleton; Gerald Langman; Simon Trotter; Marianne Nicolson; Hardy Remmen; Keith Kerr; Mahendran Chetty; Lesley Gomersall; Dean A Fennell; Apostolos Nakas; Sridhar Rathinam; Girija Anand; Sajid Khan; Peter Russell; Veni Ezhil; Babikir Ismail; Melanie Irvin-Sellers; Vineet Prakash; Jason F Lester; Malgorzata Kornaszewska; Richard Attanoos; Haydn Adams; Helen Davies; Stefan Dentro; Philippe Taniere; Brendan O'Sullivan; Helen L Lowe; John A Hartley; Natasha Iles; Harriet Bell; Yenting Ngai; Jacqui A Shaw; Javier Herrero; Zoltan Szallasi; Roland F Schwarz; Aengus Stewart; Sergio A Quezada; John Le Quesne; Peter Van Loo; Caroline Dive; Allan Hackshaw; Charles Swanton Journal: N Engl J Med Date: 2017-04-26 Impact factor: 91.245
Authors: Sheba Agarwal; Wiggert A van Cappellen; Aude Guénolé; Berina Eppink; Sam E V Linsen; Erik Meijering; Adriaan Houtsmuller; Roland Kanaar; Jeroen Essers Journal: J Cell Biol Date: 2011-02-28 Impact factor: 10.539