| Objects Hepatocellular carcinoma(HCC)is one of the most frequently diagnosed malignant diseases around the world.It is predicted to be the fourth major killer and the sixth most frequently diagnosed cancer in the world.Despite the improvement in survival of HCC patients because of advances in surgical techniques and the advent of immunotherapy,the outcome is still poor in terms of the high recurrence rate and metastasis rate of hepatocellular carcinoma patients.However,the exact mechanism by which these cancers are developed and progression remains unknown.Tyrosine metabolism is an important pathway of amino acid metabolism in the human body,mainly in the liver.Abnormal tyrosine metabolism will cause various liver diseases including HCC.Our previous study detected the abnormal expression of protein 4-hydroxyphenylpyruvate dioxygenase(HPD)in HCC by i TRAQ technology.HPD is a key enzyme in tyrosine metabolism.Here in our study,we aimed to identify the expression and the clinical significance of HPD in HCC.Methods: Western Blotting and q RT-PCR were employed to evaluate the level of HPD in hepatocarcinoma cells and fresh samples.The expression of HPD was further confirmed by immunohistochemistry(IHC)using a tissue microarray(TMA)cohort with a total of 778 HCC patients.Furthermore,the expression of HPD in HCC was evaluated using HCC m RNA expression data from TCGA databases.Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were used to determine the correlation between HPD expression and survival rate of HCC patientsResult: 1.HPD m RNA and protein expression was dramatically reduced in HCC cell lines and fresh tissue samples.2.Immunohistochemical staining HCC TMA further showed that decrease of HPD was linked to an adverse overall postoperative survival(p<0.001).3.Low expression of HPD was correlated with advanced TNM staging,vascular infiltration etc.In addition,multivariate analyses indicated that HPD was an independent predictive factor of HCC survival.4.The positive rate of HPD in HCC tumor tissues is 64.3%,and the expression of HPD is negative in liver metastatic tumors,HPD can be used for the identification of primary and metastatic tumors of the liver.Conclusions: our results suggested that HPD may serve as a valuable prognostic marker and a potential differential diagnostic marker. |
