Expression Of Gli2and FoxM1in Hepatocellular Carcinoma And Their Relationship With Clinical Prognosis

Background:Hepatocellular carcinoma (HCC) is one of the most common humanmalignancies, ranked fifth in the global cancer incidence, mortality has ranked second,and each year about690,000patients died of liver cancer[1]. Classification of livercancer with HCC in the majority, the cause of primary liver cancer include viral,alcoholic hepatitis and liver cirrhosis, aflatoxin, etc., while in China with chronichepatitis (mainly hepatitis B and C) is the main cause. At present, hepatocellularcarcinoma cure is surgical excision remains, supplemented by other treatmentmethods, such as interventional therapy, chemotherapy, radiotherapy and moleculartargeted therapy. However, due to the early symptoms of liver cancer is not obvious,the most patients when treatment is advanced, and liver cancer cells also are notsensitive to radiation and chemotherapy and postoperative recurrence, transfercharacteristics, so resulting in a shorter overall survival in HCC patients. But for HCCrecurrence, invasion and metastasis, the mechanism of the present study still not veryclear, lack of an effective molecular predictor of liver cancer recurrence andmetastasis.Hedgehog signaling pathway in cell growth, embryo formation and maintenanceof the adult tissue homeostasis plays a very important role. At the same time, moreresearch has shown that Hedgehog signals participating in a wide variety of tumorformation and development, such as basal cell carcinoma, gastrointestinal cancer,ovarian cancer, etc. Gli as a key nuclear transcription factor of Hedgehog signalingpathways, studies have reported Gli2over expression in HCC and closes links withpostoperative recurrence and metastasis of HCC. FoxM1is one of the Fox family oftranscription factors, which involves a variety of cell biological processes, such ascell differentiation, migration, invasion, DNA damage repair, tissue homeostasis,angiogenesis, inflammation and so on. Therefore, to explore the role of Gli2andFoxM1occurs in liver cancer, development and recurrence in the process is of greatsignificance. Objectives:1. To research the expression and its relationship with clinicopathologicalfeatures between the Gli2and FoxM1in HCC.2. Analyze the relationship between Gli2, FoxM1and overall survival,disease-free survival rate in HCC.3. To investigate the clinical value of Gli2-FoxM1in prediction of recurrenceand metastasis of HCC.Methods:1. The selection of clinical samplesNinety-two surgical specimens of primary HCC tissues and correspondingadjacent tissues samples obtained from the First Affiliated Hospital of NanchangUniversity, Department of Pathology between January2008to January2012.Andanother20fresh HCC tissues from the First Affiliated Hospital of NanchangUniversity, Center for Experimental Medicine after liver cancer resection of frozensamples. All selected clinical specimens taken from the adults aged18years, whowere no history of cancer, preoperative chemotherapy in patients with primaryhepatocellular carcinoma any unused lines. We fully informed patients specimenspurposes and obtained permission from the patients before use. First, we search thepatients undergoing resection of HCC, and recording informations on the patient’spathology in Pathology. Then inquire the patient’s clinical data in medical recordroom. The last of all these patients were followed up.2. The detection of Gil2and FoxM1in HCCAll specimens were reaffirmed its pathological diagnosis by HE staining.Two-step immunohistochemical detection of the expression of Gli2and FoxM1.Thenusing chi-square test, rank sum test, Spearman rank correlation analysis test, andother statistical tests to analyze the relationship between Gli2and FoxM1proteinexpression and clinicopathological parameters in HCC. 3. Patients with HCC follow upFirst, we search the patients undergoing resection of HCC, and recordinginformation on the patient’s pathology in Pathology, such as name, tumor grade,tumor size, cirrhosis, vascular invasion. Then inquire the patient’s clinical dataincluding hepatitis B infection, preoperative AFP and whether the line after TACEsurgery in medical record room. The last of all these following up the patients bytelephone and search the last admission review information and other means. Recordsthe patient’s postoperative treatment and relapse, and the time of death before in June2013.Results:1. The expression of Gli2in HCC(1). In92cases, Gli2protein showed strong expression in56.5%cases of HCC,in its corresponding normal tissues Gli2strong expression rate of4.5%, has obviousdifference in statistical significance (P <0.001); The expression of Gli2in HCCmainly concentrated in the nucleus and cytoplasm, while in normal tissues are mainlyconcentrated in the cytoplasm.(2). The expression of Gli2in HCC tissues mainly concentrated with patient’sgender, age, tumor diameter, cirrhosis of the liver, hepatitis B infection, AFP andTNM staging had no obvious correlation.(3). The expression of Gli2in HCC tissues were significantly concentrated withtumor histological grade, vascular invasion and BCLC system.2. The expression of FoxM1in HCC(1). In92cases, FoxM1protein showed strong expression in48.9%cases ofHCC, in its corresponding normal tissues Gli2strong expression rate of11.9%, hasobvious difference in statistical significance (P <0.001); The expression of FoxM1inHCC mainly concentrated in the nucleus and cytoplasm, while in normal tissues aremainly concentrated in the cytoplasm.(2). The expression of FoxM1in HCC tissues mainly concentrated with patient’sgender, age, cirrhosis of the liver, hepatitis b infection, AFP and TNM staging were not significantly correlation.(3). The expression of FoxM1in HCC tissues were significantly concentratedwith tumor diameter, tumor grade, vascular invasion and BCLC system.3. The correlation analysis between Gli2and FoxM1in HCCThe results showed that there are significant association between Gli2andFoxM1expression, the expression of both showing consistency. Expression of Gli2protein and FoxM1protein is significant positive correlation, the difference wasstatistically significant (R=0.288，P <0.05).4. Follow upThe expression of Gli2and FoxM1in HCC were related to the patient’s overallsurvival and disease-free survival. Gli2and FoxM1protein expression in patientswith overall survival and disease-free survival were significantly higher than inpatients with positive expression (P <0.05).Conclusion:Gli2and FoxM1highly expressed in hepatocellular carcinoma (HCC),suggesting that Gli2and FoxM1may participate in the development and progressionof hepatocellular carcinoma. A positive correlation between the expression of Gli2and FoxM1demonstrates that they maybe play a coordination role in the developmentof hepatocellular carcinoma. At the same time both the expression and the survival ofHCC patients is obviously relevant, suggesting that combined detection for detectionand prognosis of primary hepatocellular carcinoma (HCC) is of great significance.