Prognostic significance of sodium-potassium ATPase regulator, FXYD3, in human hepatocellular carcinoma

Abstract

The clinical significance of the sodium-potassium ATPase regulator FXYD domain-containing ion transport regulator 3 (FXYD3) has been demonstrated in a number of types of cancer. However, the role of this protein in human hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, 217 HCC tissue samples were analyzed to evaluate the expression and prognostic significance of FXYD3 in HCC. Reverse transcription-quantitative polymerase chain reaction was used to analyze the mRNA expression of FXYD3 in 80 primary HCC specimens and paired non-cancerous liver tissue samples, while western blotting was used to analyze the protein expression level of FXYD3 in another 24 pairs. These analyses demonstrated that the expression level of FXYD3 was significantly increasedb at the mRNA and protein levels in HCC tumor tissues compared with adjacent non-cancerous tissues. Immunohistochemical analysis of 137 paraffin-embedded HCC tissue samples indicated that the expression of FXYD3 was associated with HCC clinicopathological characteristics. Kaplan-Meier analysis demonstrated that patients with high FXYD3 protein expression (n=60) experienced significantly poorer overall survival time compared with patients with low FXYD3 protein expression (n=77) (P<0.001). Multivariate analysis demonstrated that FYXD3 protein expression level (hazard ratio, 2.137; 95% confidence interval, 1.224–3.732; P=0.008) was an independent prognostic factor in patients with HCC. Overall, the results indicated that FXYD3 expression levels were higher in HCC tumor tissues than in adjacent non-cancerous tissues, and that the FXYD3 protein may serve as a prognostic marker for HCC.

LncRNA LINC01503 aggravates the progression of cervical cancer through sponging miR-342-3p to mediate FXYD3 expression

“…It has been reported that FXYD3 is closely connected with the progression of various tumors [9,20,21]. However, the role of FXYD3 in CC remains unclear.…”

“…FXYD domain containing ion transport regulator 3 (FXYD3), also named as mammary tumor 8, is a part of FXYD protein family and mainly distributed in cell membrane and cytoplasm [9]. It has been reported that FXYD3 functions as a regulator of sodium-potassium ATPase [10].…”

FXYD6 overexpression in HBV-related hepatocellular carcinoma with cirrhosis

“…The family protein is a regulator of Na, K-ATPase, which plays an important role in the formation and maintenance of sodium and potassium ion transmembrane concentration gradients [ 17 ]. Meanwhile, members of the FXYD protein family such as FXYD3 and FXYD5 play an important role in the pathogenesis of numerous malignant tumors and are used as indicators for the biological characteristics and prognostic factors of certain tumors [ 18 , 19 , 20 , 21 ]. FXYD6 cDNA was first cloned in a rat hippocampus library by Yamaguchi [ 22 ], who named the encoded protein phosphohippolin, and FXYD6 protein was expressed highly in neurons and associated with neuronal cell development and synaptic signal transduction in a later research [ 6 ].…”

Comprehensive Network Analysis of the Molecular Mechanisms Associated with Sorafenib Resistance in Hepatocellular Carcinoma

“…Among them, the clinical significance of the sodium-potassium ATPase regulator FXYD domain-containing transport regulator 3 (FXYD3) has been proved to have potential regulatory effects in a variety of cancers. In hepatocellular carcinoma, it can be used as an independent prognostic factor [29]. Studies have shown that FXYD3 is a multidrug resistance gene and plays an essential role in the multidrug resistance mechanism of hepatocellular carcinoma [30].…”