A human tissue-specific transcriptomic analysis reveals a complex relationship between aging, cancer, and cellular senescence
A human tissue-specific transcriptomic analysis reveals a complex relationship between aging, cancer, and cellular senescence
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DOI：
10.1111/acel.13041
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发表时间：
2019-09-27
期刊：
影响因子：
7.8
通讯作者：
de Magalhaes, Joao Pedro
中科院分区：
文献类型：
--
作者：
Chatsirisupachai, Kasit;Palmer, Daniel;de Magalhaes, Joao Pedro
衰老是癌症的最大风险因素，但将这两个过程联系起来的机制尚不清楚。利用GTEx和TCGA数据，我们比较了9个人类组织中随年龄差异表达的基因和在癌症中差异表达的基因。在大多数组织中，衰老和癌症基因的表达模式发生了相反的变化。例外是甲状腺和子宫，我们发现在衰老和相应的癌症中，转录水平的变化是相同的。随着年龄的增长而差异表达的基因和跨组织的癌症差异表达基因之间的重叠集在几个过程中得到了丰富，主要是细胞周期和免疫系统。此外，来自荟萃分析的细胞衰老特征与人体组织中的衰老方向相同，而与癌症特征相反。因此，衰老和细胞衰老中的转录变化可能与细胞增殖减少有关，而癌症的转录变化则转向促进细胞分裂。我们的结果强调了衰老和癌症之间的复杂关系，并表明，虽然一般情况下衰老过程可能与癌症相反，但人类衰老和癌症之间的转录转录联系是组织特有的。
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.