A Novel Lipofuscin-detecting Marker of Senescence Relates With Hypoxia, Dysregulated Autophagy and With Poor Prognosis in Non-small-cell-lung Cancer.
Senescence
autophagy
glycolysis
hypoxia
lipofuscin
lung cancer
Journal
In vivo (Athens, Greece)
ISSN: 1791-7549
Titre abrégé: In Vivo
Pays: Greece
ID NLM: 8806809
Informations de publication
Date de publication:
Historique:
received:
17
07
2020
revised:
03
08
2020
accepted:
07
08
2020
entrez:
4
11
2020
pubmed:
5
11
2020
medline:
22
6
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 33144423
pii: 34/6/3187
doi: 10.21873/invivo.12154
pmc: PMC7811663
doi:
Substances chimiques
Lipofuscin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3187-3193Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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