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The Research Of Prognostic Markers For Primary Liver Cancer After Hepatectomy And Liver Transplantion

Posted on:2017-08-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:J DingFull Text:PDF
GTID:1364330503957812Subject:Surgery
Abstract/Summary:PDF Full Text Request
Hepatocellular carcinoma(HCC)is one of the most common digestive system malignant tumors.The diversity of the tumor's biological behavior and the complexity of clinical situation lead that HCC patients in the stagement who have been peformed the curative surgery went to different prognosis.Therefore,it is meaningful to evaluate the prognosis of primary liver cancer patients for clinical treatment.In this study,Two different methods were used to assess the prognosis of patients with primary liver cancer.Firstly,we tried to find the prognosis markers of patients with primary liver cancer from the genetic level.Transcriptome sequencing(RNA-seq)was used in three groups of patients in stage 0 and stage A of BCLC stagement.The three groups are group case,group control and group normal.Group case: tumor tissues from patients with tumor recurrence in half year after radical resection operation for hepatocellular carcinoma(n = 11);group control: tumor tissues from patients with no tumor recurrence for at least two years after radical resection operation for hepatocellular carcinoma a(n = 10);group normal:normal liver tissues(n=5).Sixteen differentially expressed genes were found,in which 5 genes were the subtypes of metallothionein-1.The different expression of MT-1H,MT-1M are both the most significant.This experiment has carried on the deep research to the function of the two genes.The expression of MT-1H in primary hepatocellular carcinoma was lower than that in normal liver tissues.The proliferation of hepatocellular carcinoma cells with overexpression of MT-1H was weaker than that of common hepatocellular carcinoma cells(p=0.020).Hepatocellular carcinoma cells overexpressing MT1 H had a lower rate of tumor formation in nude mice(p=0.040).The results of RT-PCR test in 99 patients' HCC tissues showed that patients with low expression of RNA for MT-1H often indicated a higher rate of tumor recurrence and a worse prognosis(p=0.023).The results of RT-PCR test in 91 patients' HCC tissues showed that patients with low expression of RNA for MT-1M often indicated a higher rate of tumor recurrence and a worse prognosis(p=0.029).And there was a correlation between the expression of MT-1M RNA and the level of AFP of patients(p=0.017).Circulating tumor cells is another prognostic marker for surgical treatment of primary hepatocellular carcinoma.In our study,peripheral blood from patients with hepatocellular carcinoma who would been peformed liver transplantation received circulating tumor cell detection which was by magnetic bead screening.The cell surface key markers were ASGPR,GPC3,and CK.The results showed that between 3 to 43 CTCs in 7.5ml peripheral blood can be detected,on average 18.52 + 8.47.But it is no statistical significance to predicted tumor recurrence and the prognosis after surgery by simplely detecting the circulating tumor cells in peripheral blood of patients with HCC.The number of circulating tumor cells in 20 patients before and after operation was detected.The increased CTCs suggested a higher tumor recurrence rate and a worse prognosis.Besides,there was a correlation between the change of circulating tumor cells before and after the surgery,and the level of AFP in patients.In this study,Two different methods were used to assess the prognosis of patients with primary liver cancer.For hepatocellular carcinoma patients,MT-1H and MT-1M were found as two prognostic genetic markers,as well as the dynamic changes of circulating tumor cells were considered as a cell marker.By the markers mentioned above,the preoperative evaluation and prediction of the prognosis of patients can be more accurate,so as to provide more effective support for the diagnosis and treatment for primary liver cancer.
Keywords/Search Tags:hepatocellular carcinoma, tumor marker, RNA-seq, circulating tumor cell
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