Identification and validation of methylation-driven genes prognostic signature for recurrence of laryngeal squamous cell
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PRIMARY RESEARCH
Cancer Cell International Open Access
Identification and validation of methylation‑driven genes prognostic signature for recurrence of laryngeal squamous cell carcinoma by integrated bioinformatics analysis Jie Cui3†, Liping Wang2†, Waisheng Zhong4†, Zhen Chen5, Jie Chen4*, Hong Yang3* and Genglong Liu1*
Abstract Background: Recurrence remains a major obstacle to long-term survival of laryngeal squamous cell carcinoma (LSCC). We conducted a genome-wide integrated analysis of methylation and the transcriptome to establish methylation-driven genes prognostic signature (MDGPS) to precisely predict recurrence probability and optimize therapeutic strategies for LSCC. Methods: LSCC DNA methylation datasets and RNA sequencing (RNA-seq) dataset were acquired from the Cancer Genome Atlas (TCGA). MethylMix was applied to detect DNA methylation-driven genes (MDGs). By univariate and multivariate Cox regression analyses, five genes of DNA MDGs was developed a recurrence-free survival (RFS)-related MDGPS. The predictive accuracy and clinical value of the MDGPS were evaluated by receiver operating characteristic (ROC) and decision curve analysis (DCA), and compared with TNM stage system. Additionally, prognostic value of MDGPS was validated by external Gene Expression Omnibus (GEO) database. According to 5 MDGs, the candidate small molecules for LSCC were screen out by the CMap database. To strengthen the bioinformatics analysis results, 30 pairs of clinical samples were evaluated by digoxigenin-labeled chromogenic in situ hybridization (CISH). Results: A total of 88 DNA MDGs were identified, and five RFS-related MDGs (LINC01354, CCDC8, PHYHD1, MAGEB2 and ZNF732) were chosen to construct a MDGPS. The MDGPS can effectively divide patients into high-risk and lowrisk group, with the area under curve (AUC) of 0.738 (5-year RFS) and AUC of 0.74 (3-year RFS). Stratification analysis
*Correspondence: [email protected]; hong‑[email protected]; lglong3@mail2. sysu.edu.cn † Jie Cui, Liping Wang and Waisheng Zhong contributed equally to this work 1 Department of Pathology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, P. R. China 3 Department of Head and Neck Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, Guangdong, P. R. China 4 Department of Head Neck Surgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410000, Hunan, P. R. China Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the
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