Comprehensive analysis of the expression of sodium/potassium-ATPase α subunits and prognosis of ovarian serous cystadenocarcinoma

Wei Huang; Yongjian Zhang; Ye Xu; Shaoyou Yang; Bing Li; Lan Huang; Ge Lou

doi:10.1186/s12935-020-01414-5

Comprehensive analysis of the expression of sodium/potassium-ATPase α subunits and prognosis of ovarian serous cystadenocarcinoma

Cancer Cell Int. 2020 Jul 14:20:309. doi: 10.1186/s12935-020-01414-5. eCollection 2020.

Authors

Wei Huang¹, Yongjian Zhang¹, Ye Xu¹, Shaoyou Yang², Bing Li¹, Lan Huang^{3

4}, Ge Lou^{1

5}

Affiliations

¹ Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081 Heilongjiang China.
² Department of Pathology, Harbin Medical University, Harbin, 150081 Heilongjiang China.
³ Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081 Heilongjiang China.
⁴ Department of Medical Oncology, Tumor Hospital of Harbin Medical University, Harbin, 150081 Heilongjiang China.
⁵ Department of Gynecology Oncology, Tumor Hospital of Harbin Medical University, 150 Haping Road, Harbin, 150081 Heilongjiang China.

Abstract

Background: Ovarian serous cystadenocarcinoma (OSC) is the most common and lethal gynecological cancer in women worldwide; however, biomarkers to diagnose and predict prognosis of OSC remain limited. Therefore, the present study aimed to investigate whether sodium/potassium adenosine triphosphate (Na⁺/K⁺-ATP)ase α-subunits (ATP1As) are helpful diagnostic and prognostic markers of OSC.

Methods: Gene expression data (RNA-Seq) of 376 patients with OSC were downloaded from The Cancer Genome Atlas (TCGA) program database. Additional databases used in our analysis included the Gene Expression Omnibus, International Cancer Genome Consortium, Genotype-Tissue Expression, the Human Protein Atlas, cBioPortal for Cancer Genomics, and Cancer Cell Line Encyclopedia.

Results: The expression levels of ATP1A1 and ATP1A3 were higher in OSC tissues than in normal ovarian tissues, whereas the expression levels of ATP1A2 and ATP1A4 were lower in OSC tissues than in normal ovarian tissues. Overexpression of ATP1A2 was significantly associated with a higher Federation of Gynecology and Obstetrics (FIGO) stage and histological grade. Increased mRNA expression of ATP1A3 was significantly associated with shorter overall survival (OS) and disease-specific survival (DSS) in patients with OSC, whereas higher expression of ATP1A4 was associated with favorable OS and DSS. Multivariate analysis showed that primary therapy outcome, residual tumor, and mRNA expressions of ATP1A3 and ATP1A4 were independent prognostic factors for both OS and DSS in patients with OSC. Moreover, ATP1A1 staining was abundant in tumor tissues. A high expression of ATP1A3 was significantly correlated with poor OS and DSS in the subgroup of patients aged ≥ 60 years and with FIGO stage III, histological grade G3, and TP53 mutation. Mutation frequencies of the ATP1As were 3-5%.

Conclusions: These results indicate that the ATP1A gene family could be potential diagnostic or prognostic markers of OSC. In addition, ATP1As may be effective therapeutic targets in the treatment of OSC.

Keywords: Adenosine triphosphate; Cystadenocarcinoma; Gene expression; Gynecology; Ovary.