Up-regulation of HDAC6 Results in Poor Prognosis and Chemoresistance in Patients With Advanced Ovarian High-grade Serous Carcinoma.
Adult
Aged
Aged, 80 and over
B7-H1 Antigen
/ genetics
Cystadenocarcinoma, Serous
/ drug therapy
Drug Resistance, Neoplasm
Female
Histone Deacetylase 6
/ antagonists & inhibitors
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ genetics
Middle Aged
Ovarian Neoplasms
/ drug therapy
Prognosis
Up-Regulation
Ovarian cancer
high-grade serous carcinoma
histone deacetylase 6
hypoxia inducible factor-1α
prognosis
programmed cell death ligand-1
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
13
11
2020
revised:
28
01
2021
accepted:
01
02
2021
entrez:
31
3
2021
pubmed:
1
4
2021
medline:
10
4
2021
Statut:
ppublish
Résumé
Ovarian high-grade serous carcinoma (HGSC) gradually acquires chemoresistance after recurrence. Our previous study on ovarian clear-cell carcinoma found histone deacetylase 6 (HDAC6) overexpression led to chemoresistance. This study aimed to evaluate HDAC6 as a predictor of chemoresistance and a therapeutic target for ovarian HGSC. The clinical significance of HDAC6 as a predictor of prognosis and chemoresistance in HGSC was immunohistochemically evaluated. In addition, expression of programmed cell death ligand-1 (PD-L1), and hypoxia-inducible factor-1α (HIF1α) were analyzed using clinical samples from 88 patients with ovarian HGSC, and their clinicopathological characteristics were reviewed. Twenty-three patients had high HDAC6 expression, 10 positive PD-L1 expression, and 33 high HIF-1α expression. HDAC6 up-regulation was correlated with not undergoing interval debulking surgery (p<0.001), incomplete surgical resection (p=0.002), and frequent occurrence of stable disease/progressive disease according to the Response Evaluation Criteria in Solid Tumors (p=0.005) criteria. On Kaplan-Meier analysis, high HDAC6 expression was significantly associated with reduced progression-free (p=0.001) and overall (p=0.008) survival. On multivariate analysis, high HDAC6 expression (hazard ratio=1.65, 95% confidence interval 1.03-2.66; p=0.039) and surgery status were independent prognostic factors of progression-free survival. PD-L1 and HIF1α expression positively correlated with that of HDAC6. HDAC6 may become a potential therapeutic target in patients with ovarian HGSC since its up-regulation is considered to be associated with a poor prognosis in patients with this cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Ovarian high-grade serous carcinoma (HGSC) gradually acquires chemoresistance after recurrence. Our previous study on ovarian clear-cell carcinoma found histone deacetylase 6 (HDAC6) overexpression led to chemoresistance. This study aimed to evaluate HDAC6 as a predictor of chemoresistance and a therapeutic target for ovarian HGSC.
PATIENTS AND METHODS
METHODS
The clinical significance of HDAC6 as a predictor of prognosis and chemoresistance in HGSC was immunohistochemically evaluated. In addition, expression of programmed cell death ligand-1 (PD-L1), and hypoxia-inducible factor-1α (HIF1α) were analyzed using clinical samples from 88 patients with ovarian HGSC, and their clinicopathological characteristics were reviewed.
RESULTS
RESULTS
Twenty-three patients had high HDAC6 expression, 10 positive PD-L1 expression, and 33 high HIF-1α expression. HDAC6 up-regulation was correlated with not undergoing interval debulking surgery (p<0.001), incomplete surgical resection (p=0.002), and frequent occurrence of stable disease/progressive disease according to the Response Evaluation Criteria in Solid Tumors (p=0.005) criteria. On Kaplan-Meier analysis, high HDAC6 expression was significantly associated with reduced progression-free (p=0.001) and overall (p=0.008) survival. On multivariate analysis, high HDAC6 expression (hazard ratio=1.65, 95% confidence interval 1.03-2.66; p=0.039) and surgery status were independent prognostic factors of progression-free survival. PD-L1 and HIF1α expression positively correlated with that of HDAC6.
CONCLUSION
CONCLUSIONS
HDAC6 may become a potential therapeutic target in patients with ovarian HGSC since its up-regulation is considered to be associated with a poor prognosis in patients with this cancer.
Identifiants
pubmed: 33788761
pii: 41/3/1647
doi: 10.21873/anticanres.14927
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
HDAC6 protein, human
EC 3.5.1.98
Histone Deacetylase 6
EC 3.5.1.98
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1647-1654Informations de copyright
Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.