Prognostic impact of molecular profiles and molecular signatures in clear cell ovarian cancer.

Autor: Schnack TH; Department of Gynecology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 København Ø, Denmark; Department of Gynecology and Obstetrics, Odense University Hospital, J.B. Winsløws Vej 4, 5000 Odense. Electronic address: Tine@henrichsen-schnack.dk., Oliveira DNP; Department of Pathology, unit of Molecular Medicine, Herlev University Hospital., Christiansen AP; Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 København Ø, Denmark., Høgdall C; Department of Gynecology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 København Ø, Denmark., Høgdall E; Department of Pathology, unit of Molecular Medicine, Herlev University Hospital.
Jazyk: angličtina
Zdroj: Cancer genetics [Cancer Genet] 2023 Nov; Vol. 278-279, pp. 9-16. Date of Electronic Publication: 2023 Aug 03.
DOI: 10.1016/j.cancergen.2023.08.001
Abstrakt: Objective: Ovarian Clear cell carcinomas (OCCC) are characterized by low response to chemotherapy and a poor prognosis in advanced stages. Several studies have demonstrated that OCCC are heterogenous entities. We have earlier identified four molecular profiles based on the mutational status of ARID1A and PIK3CA. In this study we aimed to examine the association between molecular profiles, Tumor Mutational Burden (TMB), and molecular signatures with the clinical outcome in OCCC METHODS: We identified 55 OCCC cases with corresponding data and biological tissue samples in the Danish Gynecological Cancer Database during 2005-2016. Mutational profiling and TMB were performed using the Oncomine Tumor Mutational Load Assay. Chi-square and Cox regression analyses were used. P-values < 0.05 were considered statistically significant.
Results: Mutations in the PIK3CA gene (p=0.04) and low TMB (p=0.05) were associated with disease progression. In multivariate analyses adjusted for stage, patients with tumor mutations in the ARID1A and/or PIK3CA genes had a significantly impaired Progression Free Survival (PFS) and Overall Survival (OS) compared to patients who were wildtype ARID1A and PIK3CA (undetermined subgroup) (HR= 5.42 and HR= 2.77, respectively). High TMB status was associated with an improved PFS (HR= 0.36) and OS (HR= 0.46). A trend towards an improved PFS in patients with APOBEC enrichment was observed (HR 0.45).
Conclusion: TMB-High was associated with decreased risk of progression and with an improved PFS and OS. Furthermore, OCCC with mutations in either ARID1A and/or PIK3CA genes had a significantly impaired prognosis compared to the undetermined subgroup in stage adjusted analyses.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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