PMID- 32444802 OWN - NLM STAT- MEDLINE DCOM- 20201201 LR - 20210522 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 May 22 TI - Identification of prognostic signature of non-small cell lung cancer based on TCGA methylation data. PG - 8575 LID - 10.1038/s41598-020-65479-y [doi] LID - 8575 AB - Non-small lung cancer (NSCLC) is a common malignant disease with very poor outcome. Accurate prediction of prognosis can better guide patient risk stratification and treatment decision making, and could optimize the outcome. Utilizing clinical and methylation/expression data in The Cancer Genome Atlas (TCGA), we conducted comprehensive evaluation of early-stage NSCLC to identify a methylation signature for survival prediction. 349 qualified cases of NSCLC with curative surgery were included and further grouped into the training and validation cohorts. We identified 4000 methylation loci with prognostic influence on univariate and multivariate regression analysis in the training cohort. KEGG pathway analysis was conducted to identify the key pathway. Hierarchical clustering and WGCNA co-expression analysis was performed to classify the sample phenotype and molecular subtypes. Hub 5'-C-phosphate-G-3' (CpG) loci were identified by network analysis and then further applied for the construction of the prognostic signature. The predictive power of the prognostic model was further validated in the validation cohort. Based on clustering analysis, we identified 6 clinical molecular subtypes, which were associated with different clinical characteristics and overall survival; clusters 4 and 6 demonstrated the best and worst outcomes. We identified 17 hub CpG loci, and their weighted combination was used for the establishment of a prognostic model (RiskScore). The RiskScore significantly correlated with post-surgical outcome; patients with a higher RiskScore have worse overall survival in both the training and validation cohorts (P < 0.01). We developed a novel methylation signature that can reliably predict prognosis for patients with NSCLC. FAU - Wang, Yifan AU - Wang Y AD - Institute of Cancer and Basic medicine (ICBM), Chinese Academy of Sciences, Zhejiang, China. AD - Ultrasonic Department, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang, China. AD - Ultrasonic Department, Zhejiang Cancer Hospital, Zhejiang, China. FAU - Wang, Ying AU - Wang Y AD - Department of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Wang, Ying AU - Wang Y AD - Institute of Cancer and Basic medicine (ICBM), Chinese Academy of Sciences, Zhejiang, China. AD - Department of Gynecological Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang, China. AD - Department of Gynecological Oncology, Zhejiang Cancer Hospital, Zhejiang, China. FAU - Zhang, Yongjun AU - Zhang Y AD - Institute of Cancer and Basic medicine (ICBM), Chinese Academy of Sciences, Zhejiang, China. zhangyj@zjcc.org.cn. AD - Department of Integration of Traditional Chinese and Western Medicine, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang, China. zhangyj@zjcc.org.cn. AD - Department of Integration of Traditional Chinese and Western Medicine, Zhejiang Cancer Hospital, Zhejiang, China. zhangyj@zjcc.org.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200522 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Biomarkers, Tumor) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*genetics MH - Carcinoma, Non-Small-Cell Lung/genetics/*pathology MH - Cohort Studies MH - CpG Islands MH - *DNA Methylation MH - *Databases, Genetic MH - Female MH - Follow-Up Studies MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Lung Neoplasms/genetics/*pathology MH - Male MH - Middle Aged MH - Prognosis MH - Survival Rate PMC - PMC7244759 COIS- The authors declare no competing interests. EDAT- 2020/05/24 06:00 MHDA- 2020/12/02 06:00 PMCR- 2020/05/22 CRDT- 2020/05/24 06:00 PHST- 2019/11/17 00:00 [received] PHST- 2020/04/29 00:00 [accepted] PHST- 2020/05/24 06:00 [entrez] PHST- 2020/05/24 06:00 [pubmed] PHST- 2020/12/02 06:00 [medline] PHST- 2020/05/22 00:00 [pmc-release] AID - 10.1038/s41598-020-65479-y [pii] AID - 65479 [pii] AID - 10.1038/s41598-020-65479-y [doi] PST - epublish SO - Sci Rep. 2020 May 22;10(1):8575. doi: 10.1038/s41598-020-65479-y.