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Clinical Impact Of Telomerase Transcriptase And The Subtype Of γ-glutamyl Transpeptidase Messenger RNA-H On Early Diagnosis And Prognosis Of Hepatocellular Carcinoma

Posted on:2005-06-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:C K QinFull Text:PDF
GTID:1104360152498185Subject:Hepatobiliary Surgery
Abstract/Summary:PDF Full Text Request
Objective:To investigate the expression of telomerase transcriptase and GGTmRNA-H in hepatocellular carcinoma(HCC) ,liver tissues adjacent to HCC and benign liver diseases. Compare their levels in these tissues. To investigate whether they would be efficient tumor markers in HCC. And investigate the mechanism of the abnormal expression of GGT in HCC. Research the relationship between the H-subtype gene of GGT and HCC. To evaluate the value of hTERTmRNA and GGTmRNA-H in early diagnosis of small liver cancer by inspecting the positive expression of them and AFR To investigate the relationship between hTERT , GGTmRNA-H and theclinicopathological charactertics of HCC through the different expression in HCC with different pathological type. Following up patients with chronic hepatitis , alcoholic cirrhosis and cirrhosis from other causes, investigate the significance of hTERTmRNA and GGTmRNA-H in the process of canceration of liver. To analysis the relationship between GGTmRNA-H and the size,staging of HCC,and whether it's expression is related to portal vein metastasis , intra-and extra liver metastasis of liver cancer through inspecting the expression of GGTmRNA-H in peripheral blood in HCC patients .By searching cancer cells in HCC patients blood ,to explore it's clinical significance. Our aim is to provide theoretical basis for early finding of HCC ,the selection of the treatment procedures and prognosis of HCC. To explore the relationship between hTERT and GGTmRNA-H type and their relationship to the occurrence and metastasis of primary liver cancer by combined examination of hTERT and GGTmRNA-H type.relationship between hTERT and GGTmRNA-H type and their relationship to the occurrence and metastasis of primary liver cancer by combined examination of hTERT and GGTmRNA-H type. Methods:The expression of hTERT and GGTmRNA-H type was examined using RT-PCR method in cancerous tissues and noncancerous tissues adjacent to tumors in 65 patients with HCC, in the noncancerous tissues adjacent to tumors in 13 patients with liver metastatic tumors, in 108 patients with benign liver diseases, and 6 normal control persons . hTERT and GGTmRNA-H were expressed in 86 patients with benign liver diseases , including patients with chronic hepatitis and cirrhosis , alcoholic liver diseases patients. All the 86 patients were followed up at least 12 months. To explore the relationship between GGTmRNA-H subtype and the size of HCC tumors , and portal vein metastasis ,and metastasis to other sites by examining the expression of GGTmRNA-H subtype in peripheral blood in HCC patients. Following up 41 HCC patients without metastasis for 6 months ,to explore the value of hTERT, GGTmRNA-H in peripheral blood and AFP in predicting the metastasis of HCC. Results:l.Telomerase transcriptase was positive in 16 of 20 patients with small liver cancer, the positive rate was 80.0%, and the positive rates were 88.0%(22/25) in patients with big liver cancer, 90.0%( 18/20) in patients with giant liver cancer respectively. There was no statistical significance among these three groups (p>0.05). The positive expression of GGTmRNA subtype in these three groups were 90.0%(18/20), 96.0%(24/25), and 95.0%(19/20) respectively, there was no statistical significance among them (p>0.05).2. The positive expression rate of telomerase transcriptase in liver tissues next to and distant from liver cancer were 80.0% and 33.0% respectively. There was statistical significance between the positive expression of telomerase transcriptase in liver cancer and tissues distant from the tumors (p<0.05). There was no statistical significance between the positive expression of telomerase transcriptase in liver cancer and tissues adjacent to liver cancer. But the positive expression rates of GGTmRNA-H type in liver tissues next to and distant from liver cancer were similar (P^l). Although the positive expression rates of telomerase transcriptase wererelationship with the serum levels of GGT.3. In 65 patients with primary liver cancer , GGTmRNA-H was expressed in 61 patients (93.8%), telomerase transcriptase was expressed in 56 patients (86.2%), the positive rate of serum GGT-H was 81.5%(53/65). In tissues adjacent to tumors , telomerase transcriptase was expressed in 52 patients (80.0%), serum AFP was positive in 40 patients (61.5%), ALP-I was positive in 27 patients (41.5%).In small liver cancer ,the positive rate of GGTmRNA-H was 90.0%, the positive rates of GGTmRNA-H and telomerase transcriptase in tissues adjacent to tumors was 87.5% and 80.0%,the positive rates of GGT- II , ALP-I and AFP were 50.0%,40.0%,25% respectively. The positive rates of GGTmRNA-H and telomerase transcriptase were higher than that of AFP(p<0.05). The positive rates of all the items examined above in big liver cancers were similar , there was no statistical significance.4. GGTmRNA-H in the peripheral blood was positive in 30 of the 65 HCC patients, the positive rate was 46.2%. GGTmRNA-H was not detected in the perepheral blood of patients with metastatic liver tumors, acute and chronic hepatitis, liver cirrhosis, alcoholic liver disease, obstructive jaundice, benign liver tumors and normal controls.5. GGTmRNA-H was positive in 17patients of the 40 AFP positive patients(42.5%), and in 13 patients of the 25 AFP negative patients(52.0%), there was no significant diffirence(p>0.05). There was no correlation between the positive expression of GGTmRNA-H and AFP.6. In 65 patients with primary liver cancers , GGTmRNA-H and telomerase transcriptase expressed conincidently (both positive or both negateve) in tumors and tissues adjacent to tumors in 56 patients (86.2%) and 60 patients (92.3%), the expression of the two genes correlated significantly( Y =0.385,0.396 p<0.05). The two genes expressed coincidently in tissues adjacent to tumors in 112 patients of the 114 non-primary liver cancer patients(98.2%), also correlated significantly (Y =0.406P<0.05 )7. The positive rates of hTERT expression and GGTmRNA-H subtype expression in peripheral blood in patients with intra- and extra-hepatic metastasis were higher compared with patients without metastasis(p<0.05). The positive rate of GGTmRNA-H subtype in patients with portal vein cancerous embolism was7. The positive rates of hTERT expression and GGTmRNA-H subtype expression in peripheral blood in patients with intra- and extra-hepatic metastasis were higher compared with patients without metastasis(p<0.05). The positive rate of GGTmRNA-H subtype in patients with portal vein cancerous embolism was significantly higher than those without portal vein embolism(p<0.05).8. The positive rate of AFP expression in small liver cancer was lower than that in big liver cancer (p<0.05). There was no difference among other groups.9. The occurrence rate of portal vein metastasis and extrahepatic metastasis was higher in hTERT and GGTmRNA-H positive expression group than in hTERT and GGTmRNA-H negative expression group (p<0.05). Tumor metastasis occurred similarly in patients with or without AFP expression(p>0.05)lO.In patients with benign liver diseases , 4 patients(50.0%) progressed to liver cancer with hTERT positive expression , in contrast , only lpatient(2.3%) had cancer with hTERT negative expression. There is statistical significance between them. Similarly , 4 patients progressed to liver cancer in GGTmRNA-H positive expression group, and only 1 patients had cancer in GGTmRNA-H negative expression group. There was statistical significance between them. Conclusion:1. The positive expression rate of GGTmRNA-H subtype and telomerase transcriptase was significantly higher in primary liver cancer than that in non-primary liver cancer. Combined examination of TERT and GGTmRNA-H subtype can improve the specificity of primary liver cancer diagnosis, and would of help in difference diagnosis with metastatic liver cancer. hTERT, GGTmRNA- H subtype have close relationship with the formation and development of HCC. This also confirmed the progress from liver cirrhosis to HCC.2. The combined examination of GGTmRNA-H subtype and telomerase transcriptase can avoid the disadvantage of AFP examination, and has great importance in early diagnosis of liver cancer. The rising of telomerase activity in small liver cancer plays an important role in the canceration process. The result of hTERT examination is more sensitive and more specific than AFP examination, and would be an ideal tumor marker for the early diagnosis of HCC.3. GGTmRNA-H subtype and telomerase transcriptase expressed coincidently , the expression of these two genes correlated closely in liver cancer cells. The rise of...
Keywords/Search Tags:Carcinoma, hepatocellular, GGT gene, Diagnosis, Neoplasm metastasis
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