Expression And Clinical Significance Of Keratin23in Human Hepatocellular Carcinoma

Background and objectives: Hepatocellular carcinoma (HCC) is one of the mostcommon cancers in China with a multifactorial, multistep, complex process. Multiplefactors and regulatory mechanisms are involved in carcinogenesis of tumor, in whichthe abnormal expression of some genes may play an important role. Thus, theabnormal expression of genes in carcinogenesis and development of HCC has beenpaid more attention. Keratin23(KRT23) is a newly-defined cytokeratin, which hasbeen demonstrated to be a key regulator in carcinogenesis and development of HCC.This study was aimed to validate the expression of KRT23and its clinicopathologicalfeatures and prognostic significance in HCCMethods:1.52patients who underwent curative resection for HCC at PLAgeneral hospital from September2012to September2013were included in part Ⅰ ofthis study. All the diagnosis were pathologically demonstrated. The KRT23mRNAexpression in52paired surgically removed HCC tissues (T) and correspondingadjacent non-tumor tissues (A) were analyzed by reverse transcription polymerasechain reaction (RT-PCR) while the KRT23protein expression were analyzed byimmunohistochemistry.2. Another60patients who underwent curative resection for HCC at PLA generalhospital from April2010and April2011were included in part Ⅱ of this study. Thespecimens of HCC tissue as well as the corresponding clinicopathological featureswere collected and retrospectively analyzed. Immunohistochemstry was also used toinvestigate the KRT23protein expression in HCC tissues and the relationship betweenthe KRT23expression and the corresponding clinicopathological features were analyzed by Pearson χ2. Meanwhile, the relationship between KRT23proteinexpression and postoperative survival of the HCC patients were studied throughKaplan-Meier survival analysis and Cox proportional hazard regression analysis.Results:1.The KRT23mRNA expression level in HCC tissues was significantlyhigher than that in the corresponding adjacent non-tumor tissues (P <0.05). Theimmunohistochemical staining showed that KRT23protein expression was positive inboth the HCC tissues and the corresponding adjacent non-tumor tissues in differentdegrees. The localization of KRT23protein expression was mainly in the cytoplasm ofHCC cells and it is significantly different between the HCC tissues and thecorresponding adjacent non-tumor tissues (63.4%vs25.0%，P <0.05).2.The analysis of the relationship between the KRT23protein expression and theclinicopathological features revealed that the background of liver cirrhosis,poorly-differentiated tumors, TNM staging, infiltration of liver capsule and theformation of portal vein and bile duct tumor thrombosis were associated with the highlevel of KRT23protein expression (P <0.05).Kaplan-Meier survival analysis showedthat KRT23protein expression was a prognostic factor of postoperative HCC patientswhile the Cox proportional hazard regression analysis revealed that the formation ofportal vein and bile duct tumor thrombosis and the recurrence of tumor were theindependent prognostic factors.Conclusions:1. KRT23was over-expressed in hepatocellular carcinoma in bothmRNA and protein level and may sever as a significant genetics event in thecarcinogenesis of HCC;2. The higher expression of KRT23protein in HCC tissues was significantlyassociated with higher frequency of infiltration of tumor and may serve as a newimmunohistochemical indicator to identify the postoperative overall survival of HCCpatients.