p15(INK4B) is an alternative marker of senescent tumor cells in colorectal cancer

Senescent tumor cells are nonproliferating tumor cells which are closely related to cancer progression by secreting senescence-related molecules, called senescence-associated secreting phenotypes. Therefore, the presence of senescent tumor cells is considered a prognostic factor in various cancer types. Although senescence-associated β-galactosidase staining is considered the best marker for detection of senescent tumor cells, it can only be performed in fresh-frozen tissues. p16(INK4A), a cyclin-dependent inhibitor, has been used as an alternative marker to detect senescent tumor cells in formalin-fixed paraffin-embedded tissues. However, other reliable markers to detect senescent tumor cells is still lacking. In the present study, using public single-cell RNA-sequencing data, we found that p15(INK4B), a cyclin-dependent kinase inhibitor, is a novel marker for detection of senescent tumor cells. Moreover, p15(INK4B) expression was positively correlated with that of p16(INK4A) in colorectal cancer tissues. In in vitro studies, mRNA expression of p15(INK4B) was increased together with that of p16(INK4A) in H(2)O(2)- and therapy-induced cancer senescence models. However, the mRNA level of p15(INK4B) did not increase in the oncogene-induced senescence model in primary colonic epithelial cells. In conclusion, p15(INK4B) is a potential alternative marker for detection of senescent tumor cells together with conventional markers in advanced stages of colorectal cancer.