Abstract
BackgroundInositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) has recently been found to be implicated in the tumor progression of various cancers. However, the expression and the prognostic value of ITPKA in hepatocellular carcinoma (HCC) remains unexplored. The aim of this study is to investigate the clinical significance of ITPKA expression in HCC.MethodsWe determined the expression level of ITPKA in 135 cases of HCC tissues and the matched adjacent nontumorous tissues by quantitative real-time RT-PCR. The correlation between ITPKA expression and prognosis of HCC patients was further evaluated by univariate and multivariate analysis. Multivariate analysis of the prognostic factors was performed with Cox proportional hazards model.ResultsUp-regulation of ITPKA occurred in 48.9 % of primary HCCs compared with their nontumor counterparts (P < 0.001). In addition, high expression of ITPKA was significantly associated with vascular invasion (P = 0.001) and TNM stage (P = 0.005). Kaplan–Meier analysis showed that the 5-year overall survival (OS) and relapse-free survival (RFS) rate in the group with high expression of ITPKA is poorer than that in low expression group (32.2 and 26.8 % versus 59.2 and 57.7 %). Univariate and multivariate analyses revealed that ITPKA was an independent prognostic factor for OS and RFS. Moreover, Stratified analysis revealed that its prognostic significance still existed within the subgroup of patients with early clinical stage (TNM stage I) or normal serum AFP level (≤25 μg/L).ConclusionOur data indicated that ITPKA expression was significantly up-regulated in HCC and could serve as a potential novel prognostic biomarker for HCC patients after surgery.
Highlights
Inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) has recently been found to be implicated in the tumor progression of various cancers
ITPKA expression was up-regulated in hepatocellular carcinoma (HCC) Our prior RNA-seq profiling data showed that ITPKA was overexpressed in all ten tested HCC tumor tissues
The median fold change of ITPKA (1.84) in HCC tumor tissues was used as a cutoff value to divide all 135 patients into two groups: the high expression group (n = 66) and the low expression group (n = 69)
Summary
Inositol-1,4,5-trisphosphate-3-kinase-A (ITPKA) has recently been found to be implicated in the tumor progression of various cancers. The expression and the prognostic value of ITPKA in hepatocellular carcinoma (HCC) remains unexplored. With the advent of high-throughput sequencing technologies in recent years, transcriptome sequencing (RNA-Seq) has been a powerful tool for gene expression profiling in the study of cancer. Our group exploited a RNA-Seq to delineate differential gene expression in ten pairs of HCC and nontumor clinical samples. Overexpression of inositol-1,4,5-trisphosphate3-kinase-A (ITPKA) was observed in all ten HCC tumor tissues compared with their matched nontumoral counterparts. ITPKA is only identified in neurons and testis [6] It is one of the three inositol trisphosphate 3-kinases (ITPKs) isoforms (A, B and C) that catalyse the phosphorylation of the second messenger inositol
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