| Objective:Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death. In Asian countries, hepatitis B virus (HB V) infection is the main cause of HCC. Vaccination against HB V has reduced the incidence of HBV associated HCC. Recent studies show that Nonalcoholic fatty liver diseases (NAFLD) caused by abnormal lipid metabolism gradually become an independent risk factor for HCC. At the same time, the lipid metabolism disorders are important phenotype of tumors, which can regulate the expression of tumor associated genes.Tumor will spread to the surrounding during development, Epithelial-mesenchymal transition (EMT) are important for invasion and metastasis of tumor cells. EMT includes three types:Type 1 EMT involves primitive epithelial cells transitioning to motile mesenchymal cells, Type 2 EMT involves secondary epithelial or endothelial cells transitioning to resident tissue fibroblasts, Type 3 EMT involves epithelial carcinoma cells in primary nodules transitioning to metastatic tumor cells. Biomarkers of EMT are as follows:Cell-surface markers of EMT, such as N-cadherin, E-cadherin; Cytoskeletal markers of EMT, such as Vimentin; Extracellular proteins, such as fibronectin and laminin; Transcription factors, such as TGF-beta; microRNAs, such as miR-21.This study aims to analyze of the correlation of total cholesterol (TC), high density cholesterol (HDL-CHO), low density cholesterol (LDL-CHO) of HCC patients with HCC grading, metastasis, tumor size and HBV associated HCC. Furtherly, EMT markers are examined in HCC tissues to explore the way of abnormal cholesterol induced EMT in HCC HCC metastasis.Methods:1. Tissue Source.451 specimens are collected from Shandong Provincial Hospital affiliated to Shandong University from January 2011 to January 2015. The patients consisted of 388 men and 63 women, ranging in age from 24 to 80 years (mean ± SD,53.8 ± 26.2 years). All the HCC patients have no preoperative radiotherapy or chemotherapy before surgery. The diagnosis was confirmed histologically in all cases, based mainly on the examination of sections stained with H&E. All tumors were histologically diagnosed as HCC according to the Edmondson-Steiner classification system.2. Measurement of TC, HDL-CHO, LDL-CHO and HBsAg. Colorimetric determination was used to measure the expression of TC, HDL-CHO, LDL-CHO in hepatocellular carcinoma patients peripheral blood using the Beckman AU5800 system. Electrochemical luminescence method was used to measure the expression of HBsAg in hepatocellular carcinoma patients peripheral blood using the Roche immuno-assay system.3. Immunohistochemical staining.14 HCC specimens were chosen for IHC involving 7 from transfered group and 7 from untransferred group. The cases covered pathology grade Ⅰ, Ⅱ, Ⅲ. In the transferred group, the HCC patients had higher TC, lower HDL-CHO and higher LDL-CHO levels, In the untransferred group the HCC patients had lower TC, higher HDL-CHO and lower LDL-CHO levels. EMT markers of TGF-beta, E-cadherin, Vimentin and N-cadherin were examined by IHC.4. Statistical Analysis. SPSS13.0 was used for data analysis. Single factor analysis was used to analyze the difference between the differentiation grading groups, when there were significant differences, LSD was used for further analysis. Student t-test was applied to determine significant differences between groups. P<0.05 was considered as statistical significance.Results:1. The differences of TC, HDL-CHO and LDL-CHO between differentiation grading groups in HCC patients1) Single factor analysis was used to analyze the difference of TC between the differentiation grading groups. Analysis results (F=0.776, p=0.567> 0.05) showed no significant difference.2) Single factor analysis was used to analyze the difference of HDL-CHO between the differentiation grading groups. Analysis results (F=2.716, p=0.02<0.05) showed significant difference. LSD analysis furtherly confirmed significant difference between grade Ⅱ and Ⅲ (p=0.001< 0.05), grade Ⅱ-Ⅲ and Ⅲ (p=0.005<0.05).3) Single factor analysis was used to analyze the difference of LDL-CHO between the differentiation grading groups. Analysis results (F=0.862, p=0.506>0.05) showed no significant difference.2. The Correlation of TC, HDL-CHO and LDL-CHO with HCC metastasis1) Student t-test was applied to determine significant differences of TC between HCC transferred group and untransferred group. Analysis results (t= 1.972, p=0.049<0.05) showed significant difference.2) Student t-test was applied to determine significant differences of HDL-CHO between HCC transferred group and untransferred group. Analysis results (t=86.92, p=0.038<0.05) showed significant difference.3) Student t-test was applied to determine significant differences of LDL-CHO between HCC transferred group and untransferred group. Analysis results (t=2.057, p=0.043<0.05) showed significant difference.4) Due to samples selection and sample quantity, we temporarily did not find significant difference of TGF-β、E-cadherin、 Vimentin、 N-cadherin expression between two groups.3. The differences of TC, HDL-CHO and LDL-CHO between large HCC and small HCC1) Student t-test was applied to determine significant differences of TC between large HCC and small HCC. Analysis results (t=1.268, p=0.04206>0.05) showed no significant difference.2) Student t-test was applied to determine significant differences of HDL-CHO between large HCC and small HCC. Analysis results (t=1.954, p=0.051>0.05) showed no significant difference.3) Student t-test was applied to determine significant differences of LDL-CHO between large HCC and small HCC. Analysis results (t=1.705, p=0.089>0.05) showed no significant difference.4. The differences of TC, HDL-CHO and LDL-CHO between HBV associated HCC and non-HBV associated HCC1) Student t-test was applied to determine significant differences of TC between HBV associated HCC and non-HBV associated HCC. Analysis results (t=0.148, p=0.883>0.05) showed no significant difference.2) Student t-test was applied to determine significant differences of HDL-CHO between HBV associated HCC and non-HBV associated HCC. Analysis results (t=1.236, p=0.218>0.05) showed no significant difference.3) Student t-test was applied to determine significant differences of LDL-CHO between HBV associated HCC and non-HBV associated HCC. Analysis results (t=0.125, p=0.901>0.05) showed no significant difference.Conclusions:1. There is positive correlation of HDL-CHO with HCC differentiation grading.2. There is positive correlation of TC with HCC metastasis.3. There is negative correlation of HDL-CHO with HCC metastasis.4. There is positive correlation of LDL-CHO with HCC metastasis. |
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