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

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.

ATPase Activity of the Subcellular Fractions of Colorectal Cancer Samples under the Action of Nicotinic Acid Adenine Dinucleotide Phosphate

“…We found that the activity of this pump in cancer tissues was about 20% higher than in control samples, but this increase was not statistically significant. However, observed tendency to increasing the activity of Na + /K + ATPase in cancer is in agreement with findings of other authors, showing that the baseline expression and activity of Na + /K + ATPase were enhanced in breast cancer, compared to a non-tumorigenic breast cell line [ 21 ], in patients with ovarian serous cystadenocarcinoma [ 22 ]. In samples of patients’ colorectal cancer, highly expressed Na + /K + ATPase isozymes were found [ 23 ].…”

Identification of Potential Biomarkers for Progression and Prognosis of Bladder Cancer by Comprehensive Bioinformatics Analysis

“…Previously, ATP1A2 expression was found to be downregulated in breast cancer [ 28 ]. Another evidence for the participation of ATP1A2 in ovarian serous cystadenocarcinoma pathophysiology comes from Huang et al, which revealed that the expression of ATP1A2 was higher in adjacent normal bladder tissues than in tumor tissues [ 29 ]. Additionally, Zhang et al found that ATP1A2 was regulated by the lncRNA FLJ42875 in laryngeal squamous cell carcinoma [ 30 ].…”

Identification of Three Potential Prognostic Genes in Platinum-Resistant Ovarian Cancer via Integrated Bioinformatics Analysis

“…For example, Huang et al reported that the overexpression of ATP1A2 may be related to the poor prognosis of advanced ovarian cancer. 16 Moreover, (+)-Strebloside, a cardiac glycoside that inhibits the activity of Na + /K + -ATPase, inhibits p53 expression and NF-κB activity, inducing ovarian cancer cell apoptosis and impairing its proliferation. 17 Another evidence for the participation of Na + /K + -ATPase in ovarian cancer pathophysiology comes from Tummala et al, which revealed…”