Abstract

BackgroundOvarian 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.MethodsGene 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.ResultsThe 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%.ConclusionsThese 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.

Highlights

  • Ovarian serous cystadenocarcinoma (OSC) is the most common and lethal gynecological cancer in women worldwide; biomarkers to diagnose and predict prognosis of OSC remain limited

  • The patients were divided into four groups according to the primary therapy outcome: progressive disease (PD), 27 (8.9%); partial response (PR), 43 (14.1%); stable disease (SD), 22 (7.2%); and complete response (CR), 213 (69.8%)

  • We found that the high expression of ATP1A2 (HR = 1.48, confidence interval (CI) 1.02– 2.15, p = 0.039) and ATP1A3 (HR = 2.23, CI 1.54–3.24, p < 0.001) was significantly associated with poor overall survival (OS) in patients aged ≥ 60 years old, whereas no such correlation was observed with ATP1A1 (HR = 1.15, CI 0.80–1.65, p = 0.460)

Read more

Summary

Introduction

Ovarian serous cystadenocarcinoma (OSC) is the most common and lethal gynecological cancer in women worldwide; biomarkers to diagnose and predict prognosis of OSC remain limited. Identification of biomarkers for early diagnosis and prognosis prediction of OSC remains a crucial clinical challenge of important clinical significance. Sodium/potassium adenosine triphosphate ­(Na+/K+ATP)ase (ATP1A) is a type of ubiquitous transmembrane protein expressed widely in mammalian cells, and it plays an important role in maintaining the electrochemical gradient across the cell membrane [5]. It mainly comprises a catalytic α subunit and a regulatory β subunit. Different combinations of α and β subunits can form different subtypes of ­Na+/K+-ATPase, and their distribution is tissue specific

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call