Levels of telomerase in cancer are contingent on senescence and inflammation at bulk tissue and single-cell spatial resolution

Abstract

Telomerase activity plays a critical role in tumor growth and is quantified based on its level of expression. However, how these levels are associated with different pathways across various cancer types remains elusive due to the lack of a classification schema. Here, we defined an unsupervised learning metric for the quantitative measurement of telomerase activity and robustly classified the samples into low and high telomerase groups across different cancers. Using this classification system, we analyzed the data for over 9000 bulk tumors, single cells, and spatially organized tissues, and we found that telomerase high groups across the majority of cancers are strongly associated with genomic instability. On the contrary, lower group of telomerase across various cancers are significantly associated with cellular senescence, inflammation, ROS, and MAPK pathway activities. Cellular senescence, a hallmark of cellular aging, was dominant in older adults over the high telomerase levels in the majority of cancers, normal tissues, and human development phases. Our study comprehensively illustrates that lower levels of telomerase are associated with senescence-phenotype in the majority of cancers, which is strongly favorable for better survival outcomes.