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Open AccessArticle

Methylation-Based Classification of Cervical Squamous Cell Carcinoma into Two New Subclasses Differing in Immune-Related Gene Expression

Research Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen 518055, China
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3607;
Received: 2 October 2018 / Revised: 12 November 2018 / Accepted: 13 November 2018 / Published: 15 November 2018
Cervical cancer is traditionally classified into two major histological subtypes, cervical squamous cell carcinoma (CSCC) and cervical adenocarcinoma (CA). However, heterogeneity exists among patients, comprising possible subpopulations with distinct molecular profiles. We applied consensus clustering to 307 methylation samples with cervical cancer from The Cancer Genome Atlas (TCGA). Fisher’s exact test was used to perform transcription factors (TFs) and genomic region enrichment. Gene expression profiles were downloaded from TCGA to assess expression differences. Immune cell fraction was calculated to quantify the immune cells infiltration. Putative neo-epitopes were predicted from somatic mutations. Three subclasses were identified: Class 1 correlating with the CA subtype and Classes 2 and 3 dividing the CSCC subtype into two subclasses. We found the hypomethylated probes in Class 3 exhibited strong enrichment in promoter region as compared with Class 2. Five TFs significantly enriched in the hypomethylated promoters and their highly expressed target genes in Class 3 functionally involved in the immune pathway. Gene function analysis revealed that immune-related genes were significantly increased in Class 3, and a higher level of immune cell infiltration was estimated. High expression of 24 immune genes exhibited a better overall survival and correlated with neo-epitope burden. Additionally, we found only two immune-related driver genes, CARD11 and JAK3, to be significantly increased in Class 3. Our analyses provide a classification of the largest CSCC subtype into two new subclasses, revealing they harbored differences in immune-related gene expression. View Full-Text
Keywords: methylation; cervical cancer; classification; immune; neo-epitopes methylation; cervical cancer; classification; immune; neo-epitopes
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MDPI and ACS Style

Li, X.; Cai, Y. Methylation-Based Classification of Cervical Squamous Cell Carcinoma into Two New Subclasses Differing in Immune-Related Gene Expression. Int. J. Mol. Sci. 2018, 19, 3607.

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