Abstract
Cancers are known to be associated with accelerated aging, but to date, there has been a paucity of systematic and in‐depth studies of the correlation between aging and cancer. DNA methylation (DNAm) profiles can be used as aging markers and utilized to construct aging predictors. In this study, we downloaded 333 paired samples of DNAm, expression and mutation profiles encompassing 11 types of tissues from The Cancer Genome Atlas public access portal. The DNAm aging scores were calculated using the Support Vector Machine regression model. The DNAm aging scores of cancers revealed significant aging acceleration compared to adjacent normal tissues. Aging acceleration‐associated mutation modules and expression modules were identified in 11 types of cancers. In addition, we constructed bipartite networks of mutations and expression, and the differential expression modules related to aging‐associated mutations were selected in 11 types of cancers using the expression quantitative trait locus method. The results of enrichment analyses also identified common functions across cancers and cancer‐specific characteristics of aging acceleration. The aging acceleration interaction network across cancers suggested a core status of thyroid carcinoma and neck squamous cell carcinoma in the aging process. In summary, we have identified correlations between aging and cancers and revealed insights into the biological functions of the modules in aging and cancers.
Highlights
Cancers are known to be associated with accelerated aging, but to date, there has been a paucity of systematic and in-depth studies of the correlation between aging and cancer
The results of the enrichment analysis showed that mutation-related differential expression modules in head and neck squamous cell carcinoma (HNSC), kidney papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), prostate adenocarcinoma (PRAD) and thyroid carcinoma (THCA) were significantly enriched into Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (Table S6) and mutation-related differential expression modules in HNSC, KIRP, LIHC, LUAD, PRAD and THCA were significantly enriched to Gene Ontology (GO) biological process (BP) terms (Table S7)
The differential expression modules in bladder urothelial carcinoma (BLCA), HNSC, KIRP and THCA were significantly enriched for the GO BP term ‘cell–cell signaling’ (GO: 0007267), which is involved in any process that mediates the transfer of information from one cell to another and always carried out in the living body
Summary
Cancers are known to be associated with accelerated aging, but to date, there has been a paucity of systematic and in-depth studies of the correlation between aging and cancer. Abbreviations BLCA, bladder urothelial carcinoma; BP, biological process; BRCA, breast invasive carcinoma; COAD, colon adenocarcinoma; DNAm, DNA methylation; eQTL, expression quantitative trait locus; ESCA, esophageal carcinoma; FDR, false discovery rate; GO, Gene Ontology; GSEA, Gene Set Enrichment Analysis; HNSC, head and neck squamous cell carcinoma; KEGG, Kyoto Encyclopedia of Genes and Genomes; KIRC, kidney clear cell carcinoma; KIRP, kidney papillary cell carcinoma; LASSO, least absolute shrinkage and selection operator; LIHC, liver hepatocellular carcinoma; LOOCV, leave-one-out cross validation; LUAD, lung adenocarcinoma; mRMR, minimum redundancy maximum relevance; MSE, mean square error; PRAD, prostate adenocarcinoma; ROC, receiver operating characteristic; SVD, singular value decomposition; SVM, Support Vector Machine; THCA, thyroid carcinoma. Accelerated aging patterns across cancer types several important tumor-associated signaling pathways have been identified as frequently genetically altered in cancers, such as the cell cycle, Hippo and Myc pathways [6,7]. Age-associated DNA methylation changes have been widely reported across multiple tissues and blood [12], so quite a few researchers have emphasized integrating methylation data of multiple tissues to predict age (groups), and this has demonstrated remarkable accuracy [10,13]
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