Postoperative Survival Of Hepatocellular Carcinoma Patients Research Articles

Portal Venous and Hepatic Arterial Coefficients Predict Post-Hepatectomy Overall and Recurrence-Free Survival in Patients with Hepatocellular Carcinoma: A Retrospective Study.

The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy. HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models. Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534-2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290-1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149-2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380-2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005-2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236-2.263), higher BCLC stage (HR 1.516, 95% CI 1.300-1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198-2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060-1.997). Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients.

Profile and clinical significance of interferon gamma-inducible protein-10 (IP-10) and its receptor in patients with hepatocellular carcinoma.

Chemokines play a vital role in tumor progression, metastasis and prognosis; however, the profile and clinical significance of gamma interferon-inducible protein-10 (IP-10) and its receptor (CXCR3) in patients with hepatocellular carcinoma (HCC) have not been well evaluated. Liquid-phase chip technology was used to detect the serum IP-10 in 85 patients with HBV-related HCC, 50 patients with chronic hepatitis B (CHB) and 50 liver cirrhosis subjects (CS); simultaneously, the CXCR3 and Alpha fetoprotein (AFP) were determined. Additionally, their mRNA or protein expression levels in peripheral blood mononuclear cells (PBMC), liver tumor and paracancerous tissues were quantified using qRT-PCR or ELISA. Moreover, the IP-10 and CXCR3 expression was verified by the online data from Gene Expression Omnibus. Furthermore, the relationships of serum IP-10, CXCR3 and AFP levels with their overall survival rate were also analyzed. The levels of IP-10 and CXCR3 in HCC group were significantly higher than those in CHB and CS groups, and their mRNA of PBMC is significantly positive correlation with those in their liver tissues or HBV DNA load (P < 0.0001), respectively. The serum IP-10 and CXCR3 in HCC were significantly correlated with tumor differentiation, metastases staging and distant metastasis (P < 0.05), but not related to gender, age and tumor size (P > 0.05, except IP-10 based on age). The serum IP-10 (142.6 pg/mL) and CXCR3 (241.2 pg/mL) could be differential diagnostic surrogates that distinguish HCC from CS, and the lower IP-10 level may be conducive to the postoperative survival of HCC patients. Moreover, the IP-10 and CXCR3 would be related to anti-tumor immunity in HCC patients and be a potential target for treatment of HCC.

Tumor-suppressive role of microfibrillar associated protein 4 and its clinical significance as prognostic factor and diagnostic biomarker in hepatocellular carcinoma.

Revealing microfibrillar-associated protein 4 (MFAP4)'s function and its clinical significance in hepatocellular carcinoma (HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to evaluate MFAP4 mRNA and protein expression in paired HCC and paracarcinoma tissues, respectively. MFAP4 serum concentration was detected using enzyme-linked immunosorbent assays in healthy people (n = 30), cirrhosis (n = 15) and HCC patients (n = 80). MFAP4 protein expression was detected in two tissue microarrays (n = 60 and n = 90). Plasmids were transfected into human HCC cell line Bel-7402, and MFAP4 function was determined in vitro in cell experiments. Furthermore, tumorigenicity studies in nude mice served to assess the function of MFAP4 for HCC. Both MFAP4 mRNA and protein expression were significantly downregulated in HCC tissue compared with paracarcinoma tissue (P < 0.05). Decreased MFAP4 expression in paracarcinoma tissue was associated with poor postoperative survival in HCC patients (P = 0.027). MFAP4 was also downregulated in HCC sera compared with healthy people (P < 0.05). In vitro, MFAP4 upregulation in Bel-7402 cells induced S phase arrest, promoted apoptosis, and inhibited migration and invasion. Western blotting indicated MFAP4 overexpression increased CDK4, CDK6, pRB, P27, and BCL-XS expression. Tumorigenicity study showed that the upregulation of MFAP4 inhibited the proliferation of Bel-7402 cells in nude mice. MFAP4 expression was significantly lower both in sera and tissue of HCC patients. MFAP4 can serve as molecular marker for HCC diagnosis and prognosis. Additionally, MFAP4 acted as an important HCC tumor suppressor by inducing S phase arrest, and promoting apoptosis, cell migration, and invasion.

AGLR is a novel index for the prognosis of hepatocellular carcinoma patients: a retrospective study

BackgroundMost hepatocellular carcinoma (HCC) patients’ liver function indexes are abnormal. We aimed to investigate the relationship between (alkaline phosphatase + gamma-glutamyl transpeptidase)/lymphocyte ratio (AGLR) and the progression as well as the prognosis of HCC.MethodsA total of 495 HCC patients undergoing radical hepatectomy were retrospectively analyzed. We randomly divided these patients into the training cohort (n = 248) and the validation cohort (n = 247). In the training cohort, receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of AGLR for predicting postoperative survival of HCC patients, and the predictive value of AGLR was evaluated by concordance index (C-index). Further analysis of clinical and biochemical data of patients and the correlation analysis between AGLR and other clinicopathological factors were finished. Univariate and multivariate analyses were performed to identify prognostic factors for HCC patients. Survival curves were analyzed using the Kaplan–Meier method.ResultsAccording to the ROC curve analysis, the optimal predictive cut-off value of AGLR was 90. The C-index of AGLR was 0.637 in the training cohort and 0.654 in the validation cohort, respectively. Based on this value, the HCC patients were divided into the low-AGLR group (AGLR ≤ 90) and the high-AGLR group (AGLR > 90). Preoperative AGLR level was positively correlated with alpha-fetoprotein (AFP), tumor size, tumor-node-metastasis (TNM) stage, and microvascular invasion (MVI) (all p < 0.05). In the training and validation cohorts, patients with AGLR > 90 had significantly shorter OS than patients with AGLR ≤ 90 (p < 0.001). Univariate and multivariate analyses of the training cohort (HR, 1.79; 95% CI 1.21–2.69; p < 0.001) and validation cohort (HR, 1.82; 95% CI 1.35–2.57; p < 0.001) had identified AGLR as an independent prognostic factor. A new prognostic scoring model was established based on the independent predictors determined in multivariate analysis.ConclusionsThe elevated preoperative AGLR level indicated poor prognosis for patients with HCC; the novel prognostic scoring model had favorable predictive capability for postoperative prognosis of HCC patients, which may bring convenience for clinical management.

Surgical effect analysis of hepatocellular carcinoma with different lymphovascular invasion

Objective To compare the clinical features and surgical outcomes of hepatocellular carcinoma (HCC) combined with portal venous tumor thrombus (PVTT) and hepatic venous tumor thrombus (HVTT) or bile duct tumor thrombi (BDTT), and analyze the effects of different tumor thrombus (TT) types and different surgical methods for TT on prognosis. Methods The retrospective cross-sectional study was conducted. The clinical data of 220 HCC patients with lymphovascular invasion (LVI) who were admitted to the Affiliated Cancer Hospital of Guangxi Medical University between January 2004 and December 2014 were collected. Of 220 patients, 140 were combined with PVTT, 36 with HVTT and 44 with BDTT. According to patients′ conditions, they underwent tumor and TT resection, and tumor resection + TT removal or single TT removal. Observation indicators: (1) comparisons of clinical features of HCC patients with PVTT or HVTT or BDTT; (2) surgical and postoperative situations; (3) follow-up and survival. Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 2015. Measurement data with normal distribution were represented as ±s. Comparisons among 3 indicators were analyzed using the one-way ANOVA, and comparisons between 2 indicators were analyzed using the t test. Comparisons of count data were analyzed using the chi-square test. The survival curve and rate were respectively drawn and calculated by the Kaplan-Meier method, and the Log-rank test was used for survival analysis. Results (1) Comparisons of clinical features of HCC patients with PVTT or HVTT or BDTT: number of patients with Child-pugh A, Child-pugh B and peritoneal effusion, tumor diameter and cases with tumor capsule were respectively detected in 133, 7, 23, (10±4)cm, 91 in HCC patients with PVTT and 35, 1, 4, (9±4)cm, 27 in HCC patients with HVTT and 35, 9, 16, (6±4)cm, 15 in HCC patients with BDTT, with statistically significant differences (χ2=12.693, 10.408, F=11.300, χ2=17.188, P 0.05). ④ Of 44 HCC patients with BDTT, 24, 6 and 14 were respectively detected in type Ⅰ, Ⅱ and Ⅲ BDTTs, and median survival time, 1-, 3- and 5-year survival rates were respectively 38 months, 87.5%, 60.4%, 34.9% in type Ⅰ BDTT patients and 26 months, 83.3%, 16.7%, 0 in type Ⅱ BDTT patients and 35 months, 78.6%, 50.0%, 21.4% in type Ⅲ BDTT patients, showing no statistically significant difference in survival (χ2=5.312, P>0.05). Of 44 patients, median survival time, 1-, 3- and 5-year survival rates were respectively 38 months, 91.3%, 59.5%, 34.3% in 23 patients undergoing tumor and TT resection and 26 months, 85.7%, 35.7%, 15.3% in 21 patients undergoing tumor resection + TT removal through incising common bile duct, showing no statistically significant difference in survival (χ2=2.071, P>0.05). Conclusions HCC patients with PVTT have larger tumor diameter and worse liver dysfunction, and are prone to peritoneal effusion. HCC patients with different LVI undergo surgery. There is better prognosis in HCC patients with BDTT, and good prognosis in patients with HVTT, while poorer prognosis in patients with PVTT. The postoperative survival of HCC patients with PVTT is associated with TT type, and patients will have better prognosis after tumor resection + TT removal if TT type is confirmed earlier. The postoperative survival of HCC patients with BDTT is not associated with TT type, tumor resection + TT removal maybe prolong postoperative survival time. Key words: Carcinoma, hepatocellular; Portal venous tumor thrombus; Hepatic venous tumor thrombus; Bile duct tumor thrombus; Surgical procedures, operative; Prognosis; Overall survival rate

Protein Regulator of Cytokinesis PRC1 Confers Chemoresistance and Predicts an Unfavorable Postoperative Survival of Hepatocellular Carcinoma Patients.

Background: PRC1, a microtubules(MTs)-associated protein, is essential in the mitosis and cell cycle regulation. It has been recently linked to chemoresistance and tumorigenesis. The current study sought to explore the role of PRC1 on chemoresistance and postoperative prognosis of hepatocellular carcinoma(HCC).Methods: PRC1 was transfected into HCC cells to detect its effects of chemoresistance to 5-fluorouracil in vitro and in vivo. This study also investigated the impact of PRC1 on 5-FU-induced G2/M phase arrest and the potential molecular mechanism. Surgical specimens from HCC patients were examined immunohistochemically for PRC1 expression.Results: Ectopic expression of PRC1 significantly increased the chemoresistance, promoted the tumor growth and abrogated 5-FU-induced G2/M phase arrest via p21/p27-pRBs pathway. In clinical specimens, high expression of PRC1(immunostaining score≥3) in HCC cells predicted an unfavorable postoperative survival of HCC patients(P=0.019), especially for whom received postoperative chemotherapy(P=0.002). In multivariate Cox analyses, high PRC1 expression significantly predicted an unfavorable postoperative prognosis, not dependent of TNM stage.Conclusion: High PRC1 expression in HCC cells increased chemoresistance, attenuated 5-FU-induced apoptosis, abrogated 5-FU-induced G2/M phase arrest, and predicts an unfavorable survival, especially for the patients who received chemotherapy. PRC1 might be a novel prognostic and predictive marker and therapeutic target for HCC patients.

The preoperative alkaline phosphatase-to-platelet ratio index is an independent prognostic factor for hepatocellular carcinoma after hepatic resection.

A simple, inexpensive, and readily available prognostic index is highly needed to accurately predict the prognosis of hepatocellular carcinoma (HCC). This study aimed to develop a simple prognostic index using routine laboratory tests, alkaline phosphatase-to-platelet count ratio index (APPRI), to predict the likelihood of postoperative survival in HCC patients.A total of 246 patients with HCC undergoing curative resection were retrospectively analyzed. Cutoff point for APPRI was calculated using receiver operating characteristic curve analysis, and then the patients were divided into the low-APPRI group (APPRI ≤ 4.0) and the high-APPRI group (APPRI > 4.0). The influences of APPRI on disease-free survival (DFS) and overall survival (OS) were tested by the Kaplan–Meier method, and multivariate analysis using Cox regression. Elevated APPRI was associated with age, cirrhosis, and aspartate aminotransferase (AST) in HCC. Univariate analysis showed that APPRI > 4.0, tumor size >6 cm, multiple tumors, Barcelona-clinic liver cancer stages B to C, and AST > 40 U/L were significant predictors of worse DFS and OS. A multivariate analysis suggested that APPRI > 4.0 was an independent factor for DFS (hazard ratio [HR] = 1.689; 95% confidence interval [CI], 1.139–2.505; P = 0.009) and OS (HR = 1.664; 95% CI, 1.123–2.466; P = 0.011). Preoperative APPRI > 4.0 was a powerful prognostic predictor of adverse DFS and OS in HCC after surgery. The APPRI may be a promising prognostic marker for HCC after surgical resection.

Mitochondrial reactive oxygen species and complex II levels are associated with the outcome of hepatocellular carcinoma.

In the present study, two oxidative stress parameters, reactive oxygen species (ROS) and mitochondrial respiratory complex II, were evaluated in the mitochondria of hepatocellular carcinoma (HCC) cells to determine the association between these parameters and the carcinogenesis and clinical outcome of HCC. High levels of ROS and low levels of complex II were found to be associated with reduced post-operative survival in HCC patients using the log-rank test. Furthermore, multivariate analysis confirmed that the levels of ROS [relative risk (RR)=2.867; 95% confidence interval (CI), 1.062-7.737; P=0.038] and complex II (RR=5.422; 95% CI, 1.273-23.088; P=0.022) were independent predictors for the survival of patients with HCC. Therefore, the analysis of ROS and complex II levels may provide a useful research and therapeutic tool for the prediction of HCC prognosis and treatment.

Precore/Core Region Mutations in Hepatitis B Virus DNA Predict Postoperative Survival in Hepatocellular Carcinoma.

Hepatitis B virus (HBV) DNA is prone to mutations because of the proofreading deficiencies of HBV polymerase. We have identified hepatocellular carcinoma (HCC) survival-associated HBV mutations in the X protein region of HBV DNA. In the present study, we extend our research to assess HCC survival-associated HBV mutations in the HBV precore/core (PreC/C) region. The PreC/C region was amplified and sequenced and the HBV mutations were identified according to the NCBI database (http://www.ncbi.nlm.nih.gov/genome/5536). The relationships between the mutations in the PreC/C region and HCC survival were analyzed. Survival curves were generated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. After adjusting for clinical characteristics, the 1915, 2134, 2221, 2245 and 2288 mutational sites were identified as statistically significant independent predictors of HCC survival by multivariate survival analysis using a Cox proportional hazards model. In addition, the mutational site of 1896 was identified for its association with survival at a borderline significance level. A total of five mutations in the precore/core region were identified as independent predictors of postoperative survival in HCC patients. The analysis of HBV DNA mutations may help identify patient subgroups with poor prognosis and may help refine therapeutic decisions regarding HCC patients.

Expression of PEG10 Is Associated with Poor Survival and Tumor Recurrence in Hepatocellular Carcinoma.

PurposePaternally expressed gene 10 (PEG10), first identified as an imprinted gene, is paternally expressed and maternally silenced. In hepatocellular carcinoma (HCC), PEG10 has been identified as a potential target gene located within the amplified 7q21 locus. The purpose of this study was to investigate the expression of PEG10 protein in HCC and evaluate its prognostic significance.Materials and MethodsPEG10 protein expression was examined by immunohistochemistry in tumor tissues from 218 HCC patients undergoing curative resection. Furthermore, the relationships between PEG10 expression and clinicopathologic features or postoperative survival of HCC patients were evaluated. The median follow-up period was 119.8 months for survivors.ResultsPEG10 expression was observed in 148 of the 218 HCCs (67.9%) and was significantly correlated with younger age, female, higher Edmondson grade, microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer T-stage, and higher α-fetoprotein level. PEG10 expression was an independent predictor of early recurrence (p=0.013), and it showed an unfavorable influence on recurrence-free survival (p < 0.001). A subgroup analysis showed that among patients with α-fetoprotein ≤ 20 ng/mL (80 patients), the PEG10-positive group also showed an unfavorable influence on recurrence-free survival (p=0.002). Moreover, a multivariate survival analysis identified PEG10 as an independent predictor of shorter recurrence-free survival (p=0.005). PEG10 expression showed an unfavorable influence on overall survival (p=0.007) but was not an independent predictor of shorter overall survival (p=0.128).ConclusionPEG10 protein could be a potential biomarker predicting early recurrence and recurrence-free survival in HCC patients after curative resection, even in those with normal serum α-fetoprotein levels.

Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival.

Hepatocellular carcinoma (HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year, it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients, however, there is a high risk of recurrence in postoperative HCC. In clinical practice, there exists an urgent need for valid prognostic markers to identify patients with prognosis, hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients.

Kindlin-2: A novel prognostic biomarker for patients with hepatocellular carcinoma

The association of aberrant expression of Kindlin-2 with tumor progression has been reported in recent years. The purpose of this study was to investigate the expression of Kindlin-2 in hepatocellular carcinoma (HCC), and to evaluate its clinical and prognostic significance. The mRNA and protein levels of Kindlin-2 in HCC and adjacent non-cancerous tissues were examined by real-time PCR and western blotting. The relationships between Kindlin-2 expression, clinicopathological features and postoperative survival of HCC patients were also evaluated. Kindlin-2 expression was higher in HCC tissues as compared to adjacent non-cancerous tissues at both mRNA and protein levels (P<0.05, respectively). Positive expression of Kindlin-2 was significantly correlated with larger tumor size (P=0.034), capsular invasion (P=0.009), microvascular invasion (P=0.028) and poor prognosis of HCC patients (P<0.001). Moreover, multivariate survival analysis identified Kindlin-2 as an independent prognostic factor for overall and disease-free survival of HCC patients (P=0.018 and 0.001, respectively). Taken together, our findings suggested that Kindlin-2 was highly expressed in HCC tissues and was closely related to clinical progression. Therefore, Kindlin-2 protein could be a potential biomarker for predicting poor prognosis of HCC patients after surgery.

X protein mutations in hepatitis B virus DNA predict postoperative survival in hepatocellular carcinoma.

Hepatitis B virus (HBV) DNA is prone to mutations because of the proofreading deficiencies of HBV polymerase. The postoperative prognostic value of HBV mutations in HBV X protein (HBx) gene was assessed in HBV associated hepatocellular carcinoma (HCC) patients. The HBx gene was amplified and sequenced, the HBV mutations was identified according to NCBI database ( http://www.ncbi.nlm.nih.gov/genome/5536 ). The relationship between the HBV mutations and HCC survival was compared. Survival curves were generated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. After adjusting for clinical characteristics, the following eight mutational sites were identified as statistically significant independent predictors of HCC survival: 1383, 1461, 1485, 1544, 1613, 1653, 1719, and 1753. In addition, the following four mutational sites were identified for their association with survival at a border-line significance level: 1527, 1637, 1674, and 1762/1764. A total of 12 mutations in HBx gene region were identified as independent predictors of postoperative survival in HCC patients. The analysis of HBV DNA mutations may help identify patient subgroups with poor prognosis and may help refine therapeutic decisions regarding HCC patients.

Lymphatic vessel endothelial hyaluronan receptor-1 is a novel prognostic indicator for human hepatocellular carcinoma

Angiogenesis is an important mechanism of tumor development, growth and metastasis in hepatocellular carcinoma (HCC). The poor prognosis of HCC patients has been associated with a failure to detect recurrences following surgery. In the present study, we investigated the association between the patient characteristics and the expression of angiogenic genes to identify early biomarkers of HCC. A comprehensive angiogenic gene expression profile was obtained by paired TaqMan gene array analysis of primary HCC nodules and adjacent non-HCC liver tissue from 12 patients. A total of 14 genes were found to be differentially expressed in HCC liver nodules (>2-fold change); the genes encoding collagen type XVα1, IVα1 and IVα2 were upregulated and the genes associated with vessel growth, neuropilin 2 (NRP2) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) were downregulated. The histopathological analysis revealed that the evolution of HCC nodules from well to poorly differentiated was associated with a 5-fold decrease in LYVE-1 expression, reaching its lowest level early during the transition. The significance of this gene as a biomarker of postoperative survival was demonstrated by a 2-fold decrease in overall survival (OS) rates in the low expression group compared to the high expression group. The multivariate and univariate Cox regression analyses identified LYVE-1 expression as a significant independent prognostic parameter of OS [hazard ratio (HR)=3.067; 95% confidence interval (CI): 1.507-6.273; P=0.0021]. Thus, the results of this study suggested that LYVE-1 expression may constitute a novel early biomarker of postoperative survival in HCC patients.

The levels and clinical significances of hepatocyte growth factor in the hepatic tissue and serum of hepatocellular carcinoma

Objective To investigate hepatocyte growth factor (HGF) levels in the tissue and serum of patients with chronic hepatitis, cirrhosis or hepatocellular carcinoma (HCC), and analyze the clinical significances of HGF for HCC. Method Surgical specimens from 97 patients were collected during Dec.2003 to Aug.2008 in the Third Central Hospital.The patients were prospectively enrolled and categorized into four groups:normal subjects (n=11), chronic hepatitis B or C (n=6), cirrhosis (n=20) and HCC (n= 60) including well-differentiated (n= 21), moderately differentiated (n= 23), poorly differentiated (n= 16) specimens.N0 (n=24), N1 (n=21), N2 (n=54) and N3 (n=43) were tissues respectively removed from liver at 0, 1, 2 or 3 cm beyond the margin of tumor.HGF mRNA expression in liver tissues was determined by real-time quantitative reverse transcription- (RT)-PCR.Serum HGF levels in the other cases of normal subjects (n=20), chronic hepatitis B or C (n=20), cirrhosis (n=20) and HCC (n=57) were measured by ELISA.The Kaplan-Meier method with log-rank test was employed for survival analysis.Univariate and multivariate analyses were performed to identify prognostic factors in each group. Results The HGF mRNA in normal subjects, chronic hepatitis, cirrhosis, N3, N2, N1, N0 and HCC were 0.99(0.78-1.66), 2.15(1.06-3.40), 1.78(1.18-2.73), 4.59(2.67-8.63), 3.86(2.25-6.45)，3.12(1.59-5.74), 2.92(0.88-5.99) and 0.48(0.19-1.06) respectively.The serum concentration of HGF in the normal subjects, chronic hepatitis, cirrhosis and HCC patients were (0.31±0.05), (0.65±0.07), (1.27±0.30) and （2.06±0.66） μg/L respectively.The highest level of HGF mRNA was found in N3, while the HGF mRNA expression in HCC was ［（2.14±0.52）μg/L］ lower than that not only in the non-tumor tissues, but also in the normal control (U=196.50, P=0.03).The serum concentration of HGF was significantly higher in patients with chronic hepatitis, cirrhosis or HCC than in normal subjects.The serum HGF level of HCC was bounced after hepatectomy (t=2.70, P＜0.01).On the logistic regression analysis，the tumor numbers and Child-pugh were related with the levels of the tissue HGF mRNA and serum HGF of HCC, OR were 0.15 (95%CI：0.03-0.72, P<0.05) and 0.13 (95%CI：0.27-0.89, P<0.05), respectively.Univariate analysis using the Cox proportional hazards model in the complication groups revealed that the levels of the tissue HGF mRNA and serum HGF were significant risk factors of death for HCC, OR were 0.02 (95%CI:0.00-0.52, P<0.05) and 10.01 (95%CI:1.16-86.23, P< 0.05), respectively.On the Log-rank analysis, no statistically difference in the cumulative survival was found between the two groups categorized by median (0.49) of tissue HGF mRNA 2-ΔΔCT (χ2=0.13，P=0.72). While the HCC patients were dichotomized by their the median(0.69 μg/L) of serum HGF concentration, the death risk for the patients with higher levels of HGF was increased 2.84 fold than those with lower levels (95%CI:1.03-7.92，P<0.05). Conclusion HGF mRNA expression is decreased in tumor tissues, while its level in tumor adjacent live and serum is significantly elevated and is in association with shortened postoperative survival of HCC patients.（Chin J Lab Med,2012,35:598-603） Key words: Liver neoplasms; Carcinoma，hepatocellular; Hepatocyte growth factor; Reverse transcription-quantitative polymerase chain; Enzyme-linked immunosorbent assay

Expression of claudin 10 protein in hepatocellular carcinoma: impact on survival

To investigate the expression of claudin 10 in hepatocellular carcinoma (HCC) and the impact on angiogenesis and the postoperative survival of HCC patients. The expression of claudin 10 protein was analyzed on samples from 99 HCC patients undergoing hepatectomy with immunohistochemistry and 31 fresh specimens with Western blotting. We examined the relationship between claudin 10 expression with clinicopathological factors, microvessel density (MVD), and postoperative survival. Western blotting and immunohistochemical staining showed that claudin 10 protein was highly expressed in HCC, compared with paraneoplastic liver tissue and normal liver tissue (P<0.01). Claudin 10 protein expression levels were significantly higher in HCC specimens with microscopic venous invasion (P<0.01). MVD in HCC increased with enhanced claudin 10 expression (P<0.01). Kaplan-Meier survival analysis revealed that HCC patients with high claudin 10 expression had significantly shorter overall survival (P=0.01). Multivariate analysis showed that claudin 10 expression was an independent prognostic indicator for postoperative overall survival of HCC patients (P<0.01). Claudin 10 protein is highly expressed in HCC tissue and is closely related to angiogenesis. Claudin 10 protein could be a useful marker to predict poor prognosis of HCC patients after hepatectomy.