Correlation Of CCN2 Expression In Paracancerous Tissues With Clinicopathological Features And Prognosis In Patients With Hepatocellular Carcinoma

Objective To analyze the correlation of CCN2 expression in paracancerous tissues with clinicopathological features and prognosis in patients with hepatocellular carcinoma(HCC).It is also evaluated whether CCN2 can be used as predictor of prognosis in HCC patients.So as to provide possible theoretical support for further anti-CCN2 therapy in the comprehensive treatment of HCC.Methods 1.The clinical and pathological data of HCC patients diagnosed by pathology in the General Hospital of Ningxia Medical University from January 2010 to September 2017 were collected.2.Immunohistochemistry(IHC)was used to detect expression of CCN2 in paracancerous tissues samples of HCC patients.All the sections were independently assessed by two experienced pathologists.3.All statistical analyses were carried out using SPSS(SPSS for Mac,version 22,IBM Corporation).Pearson chi-square test and Spearman rank correlation were used to analyze the relationship between CCN2 expression and clinicopathological features,such as age,gender,liver function,T stage,tumor size,tumor differentiation,lymph node metastasis,distant metastasis and early intrahepatic recurrence.Using Log-rank to test Kaplan-Meier survival curve.The prognostic risk factors of HCC patients were analyzed by Cox proportional hazard model.Using ROC curve to compare the prognostic value of CCN2 in HCC patients after hepatectomy.Results 1.This study included 124 male(80.00%)and 31 female patients(20.00%).The average age was 55 years(range 31-82 years).During follow-up,72 patients(46.45%)were early intrahepatic recurrence and 85 patients(54.84%)died.There were 137 cases(88.39%)of hepatitis B surface antigen(HBs Ag)positive,132 cases(85.16%)of liver cirrhosis,and 90 cases(58.06%)of elevated alpha-fetoprotein(>20ng/ml),84 cases(54.19%)of tumor diameter ≤5 cm,10 cases(6.45%)with lymph node metastasis and 15 cases of distant metastasis(9.68%).According to the AJCC 8th edition of TNM staging system,82cases(52.90%)were in T stage Ⅰ-Ⅱ and 76 cases(47.10%)were in T stage Ⅲ-Ⅳ.2.According to the results of immunohistochemistry,the high expression of CCN2 was found in 93 cases(60.00%),and the low expression of CCN2 was found in 62 cases(40.00%).3.The expression of CCN2 in HCC paracancerous tissues was associated with gender(P=0.002),albumin level(P<0.001),tumor invasion of hepatic capsule(P=0.003),tumor diameter(P=0.035),T stage(P=0.018),distant metastasis(P < 0.001)and early intrahepatic recurrence(P<0.001).4.The overall survival(OS)of 155 patients were 1 to 112 months,and the median survival time was 42 months.The median OS of patients with low expression of CCN2 and high expression of CCN2 in paracancerous tissues of HCC was 84.27(95%CI: 73.05-95.50)months and 37.56(95%CI:32.32-42.80)months,respectively.The median DFS of patients with low expression of CCN2 and high expression of CCN2 in paracancerous tissues of HCC was 48.56(95%CI:40.57-56.55)months and 19.71(95%CI:16.18-23.24)months,respectively.The 1 and 3-year OS rates in low expression of CCN2 group were significantly higher than those in the high expression of CCN2 group(98.38%VS.82.79%,80.65%VS.50.53%,P<0.001).The 1 and 3-year DFS rates in low expression of CCN2 group were significantly higher than those in the high expression of CCN2 group(70.97%VS.45.16%,41.94%VS.18.28%,P <0.001).5.Univariate analysis showed that hepatic capsule invasion(P=0.008),tumor diameter(P=0.009),T stage(P=0.007),distant metastasis(P<0.001)and the high expression of CCN2(P<0.001)were poor prognostic factors for postoperative survival(All P<0.05).Multivariate analysis showed that the expression of CCN2 in paracancerous tissues(P<0.001)and distant metastasis(P=0.006)were independent risk factors for the OS of patients with HCC.6.The AUC of ROC curve for CCN2 expression in adjacent tissues to predict the prognosis of patients was 0.734(95%CI: 0.653-0.816,P < 0.001),sensitivity 0.812,specificity 0.657;AUC>0.7 indicates that the predictive value of CCN2 expression level is good.Conclusion 1.The expression of CCN2 in HCC paracancerous tissues was closely related to gender,albumin level,tumor invasion of hepatic capsule,tumor diameter,T stage,distant metastasis and early intrahepatic recurrence.The clinical characteristics of HCC patients with high expression of CCN2 were clinically associated with low level of ALB,invasion of liver capsule,tumor diameter>5 cm,advanced TNM stage,distant metastasis,and a higher likelihood of intrahepatic recurrence at early stages.2.High expression of CCN2 in paracancerous tissues is an independent risk factor of poor OS in HCC patients.HCC patients with low CCN2 expression had better prognosis in terms of overall survival.3.The expression of CCN2 in HCC paracancerous tissues can be used as a clinical marker for HCC prognostic evaluation,which provides possible theoretical support for further anti-CCN2 therapy in the comprehensive treatment of HCC.