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. 2021 Sep;15(3):181.
doi: 10.3892/mco.2021.2343. Epub 2021 Jul 3.

Klotho promoter methylation status and its prognostic value in ovarian cancer

Maryam H Al-Zahrani  1 , Fatimah M Yahya  1 , Mourad Assidi  2   3 , Ashraf Dallol  2   3 , Abdelbaset Buhmeida  2
Affiliations

Klotho promoter methylation status and its prognostic value in ovarian cancer

Maryam H Al-Zahrani et al. Mol Clin Oncol. 2021 Sep.

Abstract

Among all gynecological cancers, ovarian cancer (OC) is one of the deadliest types of cancer worldwide. Epigenetic silencing of some genes has been reported to be associated with OC. In this context, Klotho (KL) gene methylation is a promising biomarker for OC. The present study aimed to investigate the methylation profiles of KL and assess its prognostic value. A total of 63 formalin-fixed paraffin-embedded tissue samples from patients with primary OC were collected and analyzed in the present study. The methylation profiles of KL were assessed by performing DNA bisulfate treatment followed by DNA promoter methylation analysis using the MethyLight assay. The results revealed KL promoter hypermethylation in 62% of the OC cohort. Additionally, significant associations were observed between KL methylation profiles and tumor subtype (P<0.0001) and tumor site (P=0.039). Furthermore, Kaplan-Meier analysis revealed that a worse disease-specific survival was significantly associated with hypermethylated KL (P=0.03, log-rank; hazard ration, 0.58; 95% confidence interval (CI), 0.26-0.90). Cox regression multivariate analysis indicated that KL promoter methylation was an independent OC prognostic indicator (P=0.029). The current study suggested that KL may be a novel biomarker to predict prognosis in patients with OC, since patients with higher KL promoter methylation were more likely to have a poor prognosis and would therefore require frequent follow-up and integrative personalized therapeutic approaches.

Keywords: Klotho; biomarker; methylation; ovarian cancer; prognosis; survival.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
KL methylation profile status in the ovarian cancer cohort using the cut-off [unmethylated (0; 15 cases) vs. hypermethylated (1; 31 cases)] as a determinant of DSS in univariate (Kaplan-Meier) analysis. DSS, disease-specific survival; KL, Klotho; HR, hazard ratio.
Figure 2
Figure 2
KL methylation profile status in the ovarian cancer cohort using the cut-off [unmethylated (0; 17 cases) vs. hypermethylated (1; 27 cases)] as a determinant of DFS in univariate (Kaplan-Meier) analysis. DFS, disease-free survival; KL, Klotho; HR, hazard ratio.
See this image and copyright information in PMC

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