All samples were frozen to -70C immediately after surgical resection and stored in Tissue Bank, Chang Gung Medical Center until used. CD133 expression was negatively correlated with the presence of hepatitis B surface antigen (HBsAg). The unadjusted and adjusted odds Methoxamine HCl ratios were 0.337 (95%CI 0.126 – 0.890) and 0.084 (95%CI 0.010 – 0.707), respectively. On the other hand, p53 Methoxamine HCl expression was positively associated with the presence of HBsAg in univariate analysis. The unadjusted odds ratio was 4.203 (95%CI 1.110 – 18.673). Survival analysis indicated that both CD133 and p53 expression in HCC predicted poor disease-free survival (P = 0.009 and 0.001, respectively), whereas only CD133 expression predicted poor overall survival (P = EDC3 0.001). Cox proportional hazard model showed that p53 and CD133 expression were two independent predictors for disease-free survival. The hazard ratios were 1.697 (95% CI 1.318 – 2.185) and 2.559 (95% Methoxamine HCl CI 1.519 – 4.313), respectively (P 0.001 for both). Conclusion In area where HBV infection accounts for Methoxamine HCl the major attributive risk of HCC, CD133 expression in HCC was negatively associated with the presence of HBsAg, implicating a non-viral origin of CD133-positive HCC. Additionally, CD133 manifestation expected poor disease-free survival individually of p53 manifestation, arguing for Methoxamine HCl two distinguishable hepatocarcinogenesis pathways. Background Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed solid malignancy as well as the third most common cause of cancer-related death in the world [1]. The etiology of HCC is definitely multifactorial, including chronic hepatitis B computer virus (HBV) infection, chronic hepatitis C computer virus (HCV) illness, alcoholic liver disease, as well as others [2,3]. In areas where chronic hepatitis B is definitely highly common, such as Southeast Asia and sub-Saharan Africa, correspondingly higher incidence of HCC is found [4]. In contrast, in Western countries, where chronic hepatitis C and alcoholic liver disease account for the major attributable risk, lower prevalence of HCC is definitely observed. Over the past two decades, the incidence of HCC is definitely rising in Western world, probably due to improved incidence of HCV illness [5]. Other risk factors include old age, male gender, underlying chronic liver diseases, and most importantly, liver cirrhosis [6]. Aflatoxin exposure has also been linked to development of HCC in some areas [7-10]. A single mutation in codon 249 of p53 is frequently seen in this subgroup [9,10]. Because of the multifactorial etiology and heterogeneous nature of the diseases, the key molecular pathways leading to hepatocarcinogenesis remained illusive. With the help of advanced systems in genomic medicine, it is discovered that hepatocarcinogenesis involved not only multiple methods of molecular events but also heterogeneous cellular pathways [11-13]. At this stage, it is pivotal to identify major subpopulations of HCC, of which the oncogenic pathways are better defined so that a specific targeted restorative modality can be devised. CD133 is definitely a human being homologue of mouse Prominin-1, a five-transmembrane cell surface glycoprotein [14-16]. It is expressed inside a subpopulation of the CD34+ hematopoietic stem cells derived from fetal liver or bone marrow [17,18]. CD133 has been recognized in neuroepithelial cells, embryonic epithelial cells and adult immature epithelial cells [19-21]. On the other hand, CD133 is indicated in several types of tumor cells, including acute myeloid leukemia, glioblastoma, ependymoma and prostate malignancy [22-29]. It is hypothesized that malignancy can be originated and managed by a subset of malignancy stem cells [30,31]. Recently, CD133 was recognized in HCC cell lines as well as some human being HCC tissues, suggesting a stem cell source [32-34]. Additionally, CD133 manifestation in HCC is definitely associated with poor prognosis [35,36]. In Southeast Asia, however, the most important etiology for HCC is definitely HBV infection. It is unclear whether malignancy stem cells play a role in HBV-related hepatocarcinogenesis. In the present study, we investigated the clinicopathological significance of CD133 manifestation in HCC in an area endemic for HBV illness. Additionally, we examined whether CD133 expression associated with p53 over-expression in HCC, another element associated with poor prognosis [37,38]. Methods Individuals This study was carried out under authorization of the institutional review table, Chang Gung Medical Center. Under educated consent, 154 HCC individuals receiving total removal of liver tumors from July 1998 to Aug 2005 in Chang Gung Medical Center, Taiwan, were included. All samples were frozen to -70C immediately after medical resection and stored in Cells Standard bank, Chang Gung Medical Center until used. The following clinicopathological data were retrospectively examined: gender, age, HBV surface antigen (HBsAg), antibody against HCV (anti-HCV), liver cirrhosis status, alcoholism, Edmonson’s histology grading, microvascular invasion, tumor capsule, quantity of tumor, microsatellites, largest tumor size, portal vein invasion,.