The Effects Hepatic Progenitor Cell Activation On Different Pathological Types And Stem Cell Characteristics In Liver Cancer

Part1Clinical factors associated with prognosis ofpatients in different pathological subtypesBackground and Aims：While some studies suggest that liver cancer may have a common origin, the differenthistological types of liver cancer patients indicated the significant tumor heterogeneity,different recurrence, metastasis and poor prognosis.Our study aimed to identify the clinicalfeatures with different pathological subtypes and risk factors effecting survival andrecurrence,which to provide the basis for clinical prognosis and mechanism research.Methods:We retrospectively matched to collect212patients clinical data with different pathologicalsubtypes. With age, tumor size, tumor number, cirrhosis, preoperative tumor emboli as acondition of matching.106patients were diagnosed with combinedhepatocellular-cholangiocarnoma (CHC).106patients were diagnosed with hepatocellularcarcinoma(HCC).Univariable and multivariate analyses were performed to ascertain therisk factors affecting survival and recurrence,in order to explore the clinical indicators topredict the likelihood with different pathological subtypes.Results:Our study found that there was no significant difference in clinical features with differentpathological types, but the patient has a significantly different prognosis Combinedhepatocellular–cholangiocarnoma5-year survival rate was significantly lower thanhepatocellular carcinoma (29.9%vs75.5%,P＜0.001).With multivariate COX regressionanalyses found that tumor pathological transition and tumor diameter≥5cm were theindependent risk factors for recurrence. Tumor pathological transition and Microvascular invasion were the independent risk factors for survival.Conclusion:Patients with HCC and CHC both clinical features are similar after matching,but theprognosis is significantly different.Patients with different pathological types of tumors cansignificantly affect survival and recurrence after liver resection. Tumor diameter≥5cmwere the independent risk factors for recurrence and Microvascular invasion were theindependent risk factors for survival. Part2The effects hepatic progenitor activation on differentpathological types and stem cell characteristics in liver cancerBackground and aim:In first part,we found that different tumor pathological types can significantiy influence theprognosis of patients.Furthermore,patients in Combined hepatocellular-cholangiocarnoma(CHC) showed higher tumor heterogeneity. Its potential mechanism is unknown.Ourprevious research also found that non-tumor Proliferative index of reactive ductular(PIDR)and Hepatic progenitor cells(HPC) activation has significant correlation in CHC. Sowhether the different pathological types of liver cancer prognosis is determined by theexpression of different HPC and PIDR need to be further discussed.In this part,we aim toexplore the relationship between non-tumor HPC activation and the influence of tumorpathological types, relevant stem markers in the tumor tissue,as well as analyse theunderlying mechanism. Methods:Based on HPC detection (K7immunohistochemical) and PIDR detection technology,determine the different pathological type HPC activation. Further analysis ofimmunohistochemical related stem markers expression in tumor and non-tumor, includingPIDR、K7DR、Bmi-1、AFP、EpCAM in non-tumor;related stem markers and EMT-relatedtranscription factor Twist-1, Snail expression in tumor tissue.Using statistical analysiswhether there are in different pathological types and the influence of prognosis.Results:Our data showed that HPC activation and stem marker expression were significantly indifferent pathological types. Further analysis found that Bmi-1expression in non-tumorwas significantly correlated with high stem marker expression and EMT-relatedtranscription factor,including PIDR≥50%,AFP positive expression in non-tumor andEpCAM,AFP,Twist-1,Snail positive expression in tumor tissue. With univariable andmultivariate analysis,including PIDR≥50%,Bmi-1positive, in non-tumor tissue in thetumor were the independent risk factors for recurrence. However, PIDR≥50%, Bmi-1positive,EpCAM positive in non-tumor tissue and Twist-1positive expression were theindependent risk factors for survival.Conclusion:HPC activation and stem marker expression were significantly in different pathologicaltypes. PIDR≥50%,Bmi-1positive in non-tumor tissue were the independent risk factorsfor survival and recurrence. Bmi-1expression in non-tumor can observably influence theexpression of stem marker EpCAM,AFP and EMT-related transcription factorTwist-1,Snail in tumor tissue. The results indicate that HPC activation can exert influencefrom non-tumor to tumor tissue,which the mechanism can related to EMT.