Tissue-specific Cancer Susceptibility from TERT Activation: Implications for Safe Anti-aging Interventions

Abstract

Telomerase-reverse-transcriptase (TERT) plays a central role in maintaining cellular lifespan and telomere stability. However, reactivation of TERT in normal cells is also a hallmark of tumorigenesis, which means TERT can be a strategic target for anti-aging therapy while also being a risk factor that can induce cancer as a side effect. In this study, I compared TERT expression and cancer sensitivity in hepatocellular carcinoma (LIHC) and renal clear cell carcinoma (KIRC) to explore whether tissue-specific expression of TERT can provide the possibility of safe anti-aging through safe TERT. Wilcoxon rank-sum test results showed that TERT expression was significantly higher in LIHC than in KIRC (p < 2.2e-16). Cliff's Delta analysis confirmed a large effect size (δ = 0.55), indicating a clear difference in expression levels between the two tissues. Logistic regression model analysis showed TERT expression significantly increased the probability of cancer occurrence in LIHC (p = 0.045), but no such association was observed in KIRC. Also, ROC analysis showed high discriminatory power in LIHC (AUC = 0.805), but low predictive power in KIRC (AUC = 0.572). These results suggest TERT activation may contribute to cancer occurrence in liver tissue, but its oncogenic effects may be limited in kidney tissue. Tissue-specific sensitivity to TERT expression suggests safe anti-aging interventions may be possible by selectively reactivating telomerase only in tissues with low cancer risk.