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. 2019 Dec;18(6):e13041.
doi: 10.1111/acel.13041. Epub 2019 Sep 27.

A human tissue-specific transcriptomic analysis reveals a complex relationship between aging, cancer, and cellular senescence

Kasit Chatsirisupachai  1 , Daniel Palmer  1 , Susana Ferreira  1 , João Pedro de Magalhães  1
Affiliations

A human tissue-specific transcriptomic analysis reveals a complex relationship between aging, cancer, and cellular senescence

Kasit Chatsirisupachai et al. Aging Cell. 2019 Dec.

Abstract

Aging is the biggest risk factor for cancer, but the mechanisms linking these two processes remain unclear. Using GTEx and TCGA data, we compared genes differentially expressed with age and genes differentially expressed in cancer among nine human tissues. In most tissues, aging and cancer gene expression pattern changed in the opposite direction. The exception was thyroid and uterus, where we found transcriptomic changes in the same direction in aging and in their corresponding cancers. The overlapping sets between genes differentially expressed with age and genes differentially expressed in cancer across tissues were enriched for several processes, mainly cell cycle and the immune system. Moreover, cellular senescence signatures, derived from a meta-analysis, changed in the same direction as aging in human tissues and in the opposite direction of cancer signatures. Therefore, transcriptomic changes in aging and in cellular senescence might relate to a decrease in cell proliferation, while cancer transcriptomic changes shift toward enhanced cell division. Our results highlight the complex relationship between aging and cancer and suggest that, while in general aging processes might be opposite to cancer, the transcriptomic links between human aging and cancer are tissue-specific.

Keywords: cell division; geriatric oncology; oncogenesis; transcriptome; tumor.

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Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
The relationship between age‐DEGs and cancer‐DEGs. (a) Number of age‐DEGs. (b) Number of cancer‐DEGs. The full study name of TCGA projects can be found in the Table S1. (c) Fold change with age in GTEx data of cancer‐DEGs. Numbers indicate p‐values. (d) Overlap between age‐DEGs and cancer‐DEGs. Numbers represent p‐values with Benjamini–Hochberg correction. N.S. denotes nonsignificant overlap. Colors correspond to odds ratio. (e) GO enrichment analysis of significantly overlapping gene sets. The plot shows examples of significant enriched terms (p‐value with Benjamini–Hochberg correction < .1)
Figure 2
Figure 2
Overlap between cellular senescence signature genes and genes (a) down‐regulated with age, (b) up‐regulated with age, (c) down‐regulated in cancer, and (d) up‐regulated in cancer. Numbers represent p‐values with Benjamini–Hochberg correction. N.S. denotes nonsignificant overlap. Colors correspond to log2 odds ratio
See this image and copyright information in PMC

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