Expression Of ARID1A And CD133 Proteins In Hepatocellular Carcinoma And Their Significance

Background The mortality of liver cancer worldwide in all malignant tumors ranks third,according to gene mutation and cell signaling pathways is the key to solve the high HCC recurrence, accounting for the proportion of primary liver cancer in 90 % or more, which is the development and prognosis of multiple genes, multi-channel, multi-stage results of joint action. HCC early diagnosis difficult and postoperative recurrence rate high are the main obstacle to influence the prognosis of patients, although a few patients get early diagnosis and timely surgery and achieve a longer chance of survival, but generally patients with HCC mortality remains high, within 5 years after surgery recurrence and metastasis possibility of more than 80%.Therefor,according to gene mutation and cell signaling pathways is the key to solving the high recurrence rate of HCC. Many studies have confirmed that tumor suppressor genes and oncogenes plays a crucial role in the process of tumor, and some transcription proteins also play an indispensable role.Chromatin remodeling complex participates in many cellular processes and plays a key role in cell differentiation, proliferation, and DNA repair.AT-rich interactive domain containing protein 1A(ARIDl A) gene is animportant member of SWI/SNF chromatin remodeling complexes,located in human chromosome 1 lp36.11,which encodes a protein consisting of 2285 amino acid residues,and its relative molecular weight is about 240×103. Studies have confirmed that abnormal chromatin remodeling lead to gene expression disorder that cause a variety of diseases. Also reported,ARIDl A gene mutation result in the expression of protein decreased, causing ovarian cancer, endometrial cancer, stomach cancer, bladder cancer and other tumors. Studies of tumor stem cells has become a hot spot among many scholars in recent years. CD133 protein as one of the cell surface markers, is often used to detect cancer stem cells and normal stem cells,its coding gene located on chromosome 4, is a five transmembrane glycoprotein, composed of 865 amino acids, relative molecular weight of about 120×103.Studies have confirmed that CD133 protein not only express in many malignant tumors,such as gastric cancer, lung cancer, breast cancer, prostate cancer and cervical cancer, but also CD133 positive tumor cell has the characteristics of trumor initiating cell,which expression quantity cut rapidly with cell differentiation. Therefore, ARID1 A and CD133 protein may be a target in the process of HCC, and its diagnosis, treatment and prognosis is of great value.Objective To explore the correlation of ARID1 A and CD133 proteins expression with clinicopathological parameters and prognosis in HCC tissues.Method To collect 93 Surgical resection specimens of HCC and its corresponding tissue adjacent to carcinoma in 90 cases,69 cases of non-neoplastic distant tissues at the First Affiliated Hospital of Zhengzhou University from June,2009 to May 2012. And they were divided into three groups: group of liver cancer, para cancer group(distance to lesion distance <2cm), far away from the cancer group(the cancer from >5cm). The expression of protein ARID1 A and CD133 was examined by immunohistochemistry in HCC tissue, the expression of adadjacent tissues andnon-neoplastic distant tissues, and long-term follow-up,recording disease progression and death time.To analyze the relationship and significance of ARID1 A,CD133 protein expression with clinical index.To explore ARID1 A and CD133 in the relationship of the expression and clinical parameters and its significance,and the survival analysis was performed with statistical software.Results The positive expression rate of ARID1 A and CD133 protein were respectively 29.0%(27/93), 49.5%(46/93) in HCC specimens.ARID1 A expression levels in HCC were significantly lower than those in ANLT and distant cancer tissues; the expression level of CD133 protein in HCC was significantly higher than that in ANLT and distal cancer tissues.The expression of ARID1 A was correlated to tumor size, TNM stage and vascular invasion(P<0.05), and there was no significant correlation with other factors(P>0.05). The expression of CD133 was correlated with HBs Ag positive, vascular invasion, TNM stage and histological differentiation(P<0.05), and there was no significant correlation with other factors(P > 0.05),and there was no significant correlation between the expression of ARID1 A and CD133 protein(?=-0.064,P>0.05). Univariate survival analysis showed that low expression of ARID1 A and high expression of CD133 were associated with poor prognosis. In addition, tumor size, vascular invasion, histological differentiation, and cirrhosis were the risk factors for poor prognosis(P<0.05).The median disease free survival(DFS) and overall survival(OS) were 43 months and 55 months respectively in the ARID1 A positive expression group.The negative expression group was 26 months and 34 months respectively, and the difference was statistically significant(P<0.05). The median DFS and OS were 28 months and 37 months respectively in the CD133 protein positive expression group.The negative expression group was 43 months and 57 months respectively,and the difference was statistically significant(P<0.05). COX multivariate survival analysis showed that cirrhosis, differentiation degree and CD133 expression were independent factors affecting DFS(P<0.05), and liver cirrhosis, differentiation degree, ARID1 A expression andCD133 expression were independent factors affecting OS(P<0.05).Conclution The ARID1 A protein expression is correlated to tumor size, TNM staging and vascular invasion,and the positive ARID1 A expression has a better prognosis than those negative expression.The CD133 protein expression is correlated to HBs Ag positive, vascular invasion, TNM staging and tissue differentiation degree,and CD133 positive expression has a worse prognosis than those negative expression.