A Novel Lipofuscin-detecting Marker of Senescence Relates with Hypoxia, Dysregulated Autophagy and with Poor Prognosis in Non-small-cell-lung Cancer

Abstract

Background/Aim: The role of senescence in defining tumor aggressiveness at a clinical level remains obscure. A novel mixed histochemical/immunohistochemical method (SenTraGor™, STG) detecting lipofuscin accumulation allows the assessment of senescent cells in paraffin-embedded tissue material. Materials and Methods: STG expression was quantified in 98 surgically resected primary non-small-cell-lung carcinomas (NSCLC). Data were analyzed in parallel with other immunohistochemical markers related to hypoxia and autophagy. Results: Strong STG staining was noted in 36/98 cases (36.7%). High STG expression was significantly associated with high HIF1α expression and high expression of glucose (GLUT1) and monocarboxylate (MCT2) transporters, pointing to a link between senescence, hypoxia and glycolysis. High STG expression was also linked with high cytoplasmic accumulation of MAP1-LC3B, TFEB and LAMP2a, suggestive of a blockage of autophagy flux in tumors with intense senescence. Survival analysis showed a direct association with poor survival, independently of stage. Conclusion: SenTraGor™ provides a reliable methodology to detect lipofuscin accumulation in cancer cells in paraffin-embedded tissues, opening a new field for translational studies focused on senescence.