An integrative analysis of the age-associated multi-omic landscape across cancers

Kasit Chatsirisupachai,Luminita Paraoan,Peter Van Loo,Tom Lesluyes,João Pedro De Magalhães

doi:10.1038/s41467-021-22560-y

Kasit Chatsirisupachai, Luminita Paraoan + Show 3 more

Open Access

https://doi.org/10.1038/s41467-021-22560-y

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Abstract

Age is the most important risk factor for cancer, as cancer incidence and mortality increase with age. However, how molecular alterations in tumours differ among patients of different age remains largely unexplored. Here, using data from The Cancer Genome Atlas, we comprehensively characterise genomic, transcriptomic and epigenetic alterations in relation to patients’ age across cancer types. We show that tumours from older patients present an overall increase in genomic instability, somatic copy-number alterations (SCNAs) and somatic mutations. Age-associated SCNAs and mutations are identified in several cancer-driver genes across different cancer types. The largest age-related genomic differences are found in gliomas and endometrial cancer. We identify age-related global transcriptomic changes and demonstrate that these genes are in part regulated by age-associated DNA methylation changes. This study provides a comprehensive, multi-omics view of age-associated alterations in cancer and underscores age as an important factor to consider in cancer research and clinical practice.

Highlights

Age is the most important risk factor for cancer, as cancer incidence and mortality increase with age
Using multiple linear regression adjusting for gender, race, and cancer type, we found that genomic instability (GI)
Using logistic regression adjusting for gender, race and cancer type, we identified five out of 10 signalling pathways that showed a positive association with age, indicating that the genes in these pathways are altered more frequently in older patients, concordant with the increase in overall mutations and somatic copy-number alterations (SCNAs) with age (Fig. 5a, Supplementary Data 12)

Summary

Introduction

Age is the most important risk factor for cancer, as cancer incidence and mortality increase with age. Several studies have investigated molecular differences in the cancer genome in relation to clinical factors, including gender[9,10] and race[11,12]. These studies demonstrated gender- and race-specific biomarkers, actionable target genes and provided clues to understanding the biology behind the disparities in cancer incidence, aggressiveness and treatment outcome across patients from different backgrounds. Specific age-associated molecular landscapes have been reported in the cancer genome of several cancer types, for example, glioblastoma[15], prostate cancer[16] and breast cancer[17]. These studies focused mainly on a single cancer type and only on some molecular data types

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