Erschienen in:
24.11.2020 | Original Article
Pan-cancer methylation analysis reveals an inverse correlation of tumor immunogenicity with methylation aberrancy
verfasst von:
Changhee Park, Kyeonghun Jeong, Joon-Hyeong Park, Sohee Jung, Jeong Mo Bae, Kwangsoo Kim, Chan-Young Ock, Miso Kim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Se-Hoon Lee, Ju-Seog Lee, Dong-Wan Kim, Gyeong Hoon Kang, Doo Hyun Chung, Dae Seog Heo
Erschienen in:
Cancer Immunology, Immunotherapy
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Ausgabe 6/2021
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Abstract
Tumor immunogenicity is driven by various genomic and transcriptomic factors but the association with the overall status of methylation aberrancy is not well established. We analyzed The Cancer Genome Atlas pan-cancer database to investigate whether the overall methylation aberrancy links to the immune evasion of tumor. We created the definitions of hypermethylation burden, hypomethylation burden and methylation burden to establish the values that represent the degree of methylation aberrancy from human methylation 450 K array data. Both hypermethylation burden and hypomethylation burden significantly correlated with global methylation level as well as methylation subtypes defined in previous literatures. Then we evaluated whether methylation burden correlates with tumor immunogenicity and found that methylation burden showed a significant negative correlation with cytolytic activity score, which represent cytotoxic T cell activity, in pan-cancer (Spearman rho = − 0.37, p < 0.001) and 30 of 33 individual cancer types. Furthermore, this correlation was independent of mutation burden and chromosomal instability in multivariate regression analysis. We validated the findings in the external cohorts and outcomes of patients who were treated with immune checkpoint inhibitors, which showed that high methylation burden group had significantly poor progression-free survival (Hazard ratio 1.74, p = 0.038). Overall, the degree of methylation aberrancy negatively correlated with tumor immunogenicity. These findings emphasize the importance of methylation aberrancy for tumors to evade immune surveillance and warrant further development of methylation biomarker.