| Objective: Sal human-like genes (SALL) is a new stem cell markers,which showed high expression in embryonic stem cells. SALL4gene plays animportant role in the regulation of early embryonic development, organogenesis,proliferation and differentiation of embryonic stem cells. SALL4as anoncogene, is not expressed in adult normal liver but section detected in HCCpatients, and the expression had relevant to the prognosis of HCC patients.Hepatocyte nuclear factors（HNF）are transcription factors that regulatedthe expression of the liver genes, and controlled the liver cells function and thedevelopment of liver. Studies had shown that HNF family played an importantrole in the process of embryonic development and tumorigenesis, especially inhepatocellular carcinoma. But the mechanism was not very clearly, and hadbecome one of the hot spot in the field of medicine explore.In this study, the immunohistochemical staining was used to explore theexpression of SALL4and HNF-3beta, a member of HNF family, in HCCtissue, non-cancerous cirrhosis hepatic tissue and liver hemangiomasurrounding liver tissue. The correlation of both SALL4and HNF-3beta withthe clinical pathology date of HCC patients was analyzed, and the mechanismand the prognosis were discussed in the development of HCC.Methods:1The research object:126cases of HCC,44cases of adjacentnon-cancerous cirrhotic hepatic tissue and10cases of liver hemangiomasurrounding liver tissue, all the specimens were obtained from the fourthhospital of Hebei Medical University. All the patients had not taken any formof treatment measures before the operation.2Research methods: after resection all the tissues were fixed with10%of neutral formaldehyde, embedded in paraffin. The expression characteristic of SALL4and HNF-3beta were detected with immunohistochemistrytechnology, and the differences were analyzed with the expression of SALL4and HNF-3beta in the above three liver tissue. Follow-up of patients withpostoperative survival and the relationships were studied between the survivalanalysis of the clinical pathological data with SALL4and HNF-3beta inpostoperative HCC patients.Results:1Survival analysis of the clinical and pathological data in postoperative HCCpatientsAmong all the126HCC patients, the cumulative survival from one yearto five year were75.4%,58.7%,48.4%,24.6%and13.5%. Age, sex, bloodplatelet, Child classification, HBsAg, and HBeAb had no statisticaldifferences in HCC patients. AFP（χ2=25.685，P=0.000）, the diameter oftumo（rχ2=37.017，P=0.000）, the clinical stage（χ2=42.245，P=0.000）, BCLCclassification（χ2=23.194，P=0.000）, Pathological classification（χ2=19.937，P=0.000）and the Portal vein tumor thrombus（χ2=12.629，P=0.000）were thesignificant prognostic factors in HCC patients. The patients in the earlierclinical stages, earlier BCLC classification, high pathological classification,AFP between7~100μg/L, tumor diameter between3~5centimeter andwithout Portal vein tumor thrombus had the higher survival rate and longermean survival time, that the prognosis was better.2The expression of SALL4in liver tissueSALL4was not expressed in the liver tissues around hepatichemangioma, almost no expression in the adjacent non-cancerous cirrhotichepatic tissue. SALL4was partly expressed in the HCC tissue, mainly showedin the nucleus, a few in the cytoplasm, by light yellow to yellow browngranular. The expression of SALL4had no significant difference betweenliver tissues around hepatic hemangioma and adjacent non-cancerous hepatictissue （Z=-0.681，P=0.496）. But statistical difference existed between livertissues around hepatic hemangioma and in HCC tissue（Z=-2.600，P=0.009）and so between adjacent non-cancerous hepatic tissue and HCC tissue （Z=-4.730，P=0.000）. The expression of SALL4had no significantdifference in sex, age, HBsAg, HBeAb, the diameter of tumor andpathological classification. The expression of SALL4had great significantdifference in AFP, portal vein tumor thrombus. The expression of SALL4washigher in HCC patients with higher AFP（χ2=14.501，P=0.013）and portal veintumor thrombus（Z=-3.001，P=0.003）. The display of SALL4was relevantwith the clinical stage of HCC patients and was higher with later clinical stage（χ2=10.432，P=0.034）. The expression of SALL4was also relevant with theBCLC classification, and was stronger with later BCLC classification（χ2=13.670，P=0.001）. In HCC tissue, the expression of SALL4was correlationwith the prognosis of HCC patients. That the patients showed negativeexpression, weak positive expression, positive expression, and strong positiveexpression of SALL4, the mean survival time was43.8months,27.3months,22.7months,13.2months. The differences had statistical significance(χ2=26.994, P=0.000). In the HCC groups, the patients with higher expressionof SALL4usually had shorter mean survival time and worse prognosis.3Combining AFP and SALL4analyzing the prognosis of HCC patientsAmong the groups both AFP and SALL4negative, only SALL4positive,only AFP positive and both AFP and SALL4positive, the last group had theworst prognosis. The differences had statistical significance (χ2=21.833,P=0.000). In patients with positive expression of SALL4, with evaluated AFPlevel, the mean survival time of HCC patient decreased, and the differenceshad statistical significance (χ2=17.921, P=0.003). AFP had greater predictivesignificance with positive expression of SALL4patients.4The expression of HNF-3β in liver tissueHNF-3β was partly expressed in liver tissue around hepatic hemangiomaand non-cancerous cirrhosis hepatic tissue by light yellow to yellow browngranular or clump in the nucleus. HNF-3β was majority displayed in the HCCtissue in the nucleus, which showed by light yellow to yellow brown granularor clump distribution. The expression of HNF-3β had no significant differencebetween liver tissues around hepatic hemangioma and non-cancerous cirrhosis hepatic tissue（Z=-0.240，P=0.877）, but had great difference between livertissues around hepatic hemangioma and HCC tissues（Z=-4.064，P=0.000）, aswell as the expression between non-cancerous cirrhosis hepatic tissue andHCC tissue（Z=-7.053，P=0.000）. The expression of HNF-3β had nosignificant different in age, HbsAg, HBeAb, the diameter of tumor, AFP andPortal vein tumor thrombus in HCC tissue, as well as clinical stage,pathological classification and BCLC classification. The expression ofHNF-3β had significant different in Portal vein tumor thrombus（Z=-2.255，P=0.024）and sex（Z=-3.450，P=0.001）. HNF-3β was obvious in patients withPortal vein tumor thrombus and female patients. The expression of HNF-3βwas not relevant to the prognosis of HCC patients. The patients with negativeexpression, weak positive expression, positive expression, and strong positiveexpression of HNF-3β, the mean survival time was28.8months,26.7months,38.6months,34.8months. The differences had no statistical significance (χ2=3.834, P=0.280).5Combining AFP and HNF-3β analyzing the prognosis of HCC patientsAmong the groups both AFP and HNF-3β negative, only HNF-3βpositive, only AFP positive and both AFP and HNF-3β positive, the meansurvival time had no differences (χ2=3.116, P=0.374). Combining AFP andHNF-3β had no impact on the prognosis of patients. In patients with positiveexpression of HNF-3β, AFP was relevant to the prognosis of patients (χ2=22.095, P=0.001). Patients with higher AFP level had shorter mean survivaltime and worse prognosis, which had no difference with only AFP that hadimpact on the prognosis of patients.6Cox Regression survival analysis of HCC patientsSALL4（Wald=4.868，P=0.027）, clinical stage（Wald=7.849，P=0.005）,pathological classification（Wald=8.520，P=0.004）and AFP（Wald=3.905，P=0.048）were relevant to the prognosis of patients, there was statisticalsignificance（χ2=67.467, P=0.000）. BCLC classification（Wald=0.073，P=0.787）, the diameter of tumor（Wald=0.368，P=0.544）, portal vein tumorthrombus（Wald=0.057，P=0.812）had no relevant to the prognosis of patients. Conclusions:1The expression of SALL4in HCC tissue was greatly stronger than thatin hepatic tissue around hepatic hemangioma, non-cancerous cirrhosis hepatictissue. The difference had statistical significance. SALL4expression washigher in HCC tissue with higher AFP, portal vein tumor thrombus, laterclinical stage and BCLC classification. The expression of SALL4was relevantto the prognosis of HCC patients. The stronger the SALL4expressed, theshorter the mean survival time, and the worse prognosis of patients.2The expression of HNF-3β in HCC tissue was greatly stronger than thatin hepatic tissue around hepatic hemangioma, non-cancerous cirrhosis hepatictissue. The difference had statistical significance. HNF-3β expression wasrelevant to portal vein tumor thrombus and sex, and was stronger in patientswith portal vein tumor thrombus and was higher with female patients. Thestrong expression of HNF-3β had relationship with the generation of HCC, buthad no relevance to the prognosis of HCC patients. |
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