The Correlation Study On PinX1and Clinical Pathological Characteristics Of Hepatic Carcinoma

BackgroundTumor invasion and metastasis is a complex and orderly, multi-stage biological process affected by a number of gene regulation. Many studies have found the existence of tumor genome genetic instability, prone to microsatellite instability (microsatellite instability, MSI) and loss of heterozygosity (loss of heterozygosity, LOH). Pinx1(Pin2/TRF1-interacting protein) is the new telomerase/telomere regulatory factor found in the human and yeast cells in recent years, chromosome8p23is a point of high frequency loss of heterozygosity in a variety of tumors. It was found that the over expression of tumor cells PinX1or PinX1-TID can inhibit telomerase activity and telomere shortening in vitro and vivo tumorigenicity experiments of nude mice. The absence of endogenous PinX1can increase telomerase activity and extended telomeres, but also increase the occurrence of tumors in nude mice. Through the study of cancer of kidney, ovarian and lung, we found Pinxl in cancer tissues was significantly lower than in adjacent normal tissue, which indicates PinXl genes may be involved in controlling cell proliferation. Transform the PinX1genes into SMMC-7721hepatic carcinoma cells and found that the cell growth was inhibited significantly, which indicates PinXl gene have the function of inhibiting the growth of hepatic carcinoma cell, but the study of PinXl about LOH,MSI and protein expression in hepatic carcinoma are also rare reported. In this paper, the study of PinXl genetic instability, protein expression and liver cancer clinical pathological features will provide a theoretical basis for analyzing the occurrence and development of the Pinx1gene in hepatic carcinoma and the mechanism of action about how they affect hepatic carcinoma.ObjectiveResearch the microsatellite instability and loss of heterozygosity of Pinx1gene D8S277for hepatic carcinoma, and how does this genetic instability in hepatocellular carcinoma influence Pinxl protein on expression. Clarify the relationship of the Pinx1genetic instability and the occurrence,development of hepatic carcinoma, which provides a theoretical basis to reveal the mechanism of Pinxl as a tumor suppressor gene in tumor development. Methods(1) Envision immunohistochemistry was used to detect the expression of Pinx1protein.(2) Image-pro Plus image analysis software was used to analyze protein expression.(3) phenol-chloroform extraction method for extracting DNA from paraffin-embedded HCC tissue.(4) PCR-single strand conformation polymorphism (SSCP), conventional silver staining to analyze the Pinx1genetic instability of the D8S277locus.(5) SPSS statistic software analyzed the correlation among experimental results.Results1) The LOH detection rate of Pinx1gene D8S277microsatellite locus in hepatic carcinoma is35.71%(10/28), which has no correlation with the lymph node metastasis, with or without capsular infiltration, tumor differentiation and stage (P>0.05).2) The MSI detection rate is10.71%(3/28), which has no correlation with degree of differentiation, lymph node metastasis, stage and With or without capsular infiltration (P>0.05).3) Pinx1positive protein highly expressed in the adjacent normal tissue, low or even no expression in tumor tissue,The detection rate is32.14%(9/28), which has no correlation with degree of differentiation, lymph node metastasis and stage (P>0.05), But has significant correlation with the staging and the presence of capsular invasion (P<0.05);4) In addition, MSI and LOH of microsatellite D8S277locus has no significant difference with the Pinx1protein expression (P>0.05).ConclusionsPinx1protein expression significantly decreased in HCC tissues, There is a significant correlation between Pinx1protein expression and tumor capsule invasion. It is an important factor in inhibition of tumor development. MSI and LOH of microsatellite D8S277locus has no significant correlation with Pinx1protein expression and clinical pathological characteristics of hepatic carcinoma. Which maybe not the main affect mechanism of Pinx1protein expression and the development of liver cancer, there may be exist other effects mechanism. Pinx1may played a role in inhibit liver cancer development, but not a major factor.