HBV感染对胰腺癌恶性潜能和临床不良预后的影响及其机制研究

乙肝病毒（HBV）感染诱发原发性肝癌已为人熟知，非何杰金氏淋巴瘤的发病也被证实与HBV感染有关。近年来，包括本单位在内的多个国内、外研究中心在胰腺癌病人的血清及组织样本中发现了一系列HBV感染的证据，并通过临床回顾性分析证实与胰腺癌发生有关，但至今仍缺少实验证据。预实验中我们建立了胰腺癌成瘤及转移的体内、外模型，开展了慢病毒转染及基因敲除等功能实验，首次在基础水平证实了HBV感染不但促进胰腺癌恶性转化，还增加其转移潜能；并且促癌效应高度依赖于胰腺癌细胞内突变型Kras基因的存在。为进一步阐释胰腺癌内HBV感染激活的特定分子机制，我们拟开展高通量的蛋白或基因芯片筛选，结合生物信息学分析，确认HBV感染后胰腺癌细胞内出现差异表达的基因谱及分子信号，并作临床多中心、大样本的验证。最终建立反映HBV阳性或阴性胰腺癌特殊生物学表型、临床病理特征、疾病转归和传统治疗疗效的分子分型，指导临床个体化治疗。

The relationship between tumor development and virus infection has been pay attention to continuously by oncologist. It is well-known that hepatitis B virus (HBV) infection induces tumorgenesis and progression of hepatocellular carcinoma (HCC). Also the tumor-promoting role of HBV in another tumor, non-Hodgkin's lymphoma, has been confirmed. Recently, growing studies detected certain HBV antigens and HBV-DNA in pancreatic juice or pancreatic tissue. Serveral publications came from clnical retrospective studies have even suggested a close link between HBV-related serum markers and pancreatic cancer development. Inspired by these, I and my colleagues have pioneered in vitro and in vivo research based on tumor formation or metastasis model to better understand the role of HBV infection in pancreatic cancer development. The results show that HBV infection not only contributes to pancreatic tumorigensis, but also promotes tumor parogression. More importantly, the enhanced aggressiveness due to HBV infection in pancreatic cancer cells is highly dependent on the presence of mutant Kras. These findings suggest a distinct tumor-promoting mechanism of HBV infection in pancreatic cancer. Accordingly, we are being applied high-throughput screenings together with bioinformatics technologies to identify the pivot gentic signature or signaling pathway in pancreatic cancer cell induced by HBV infection. It expects to reveal an unique tumor-promoting mechanism of HBV infection in pancreatic cancer and subsequently to identify novel targets for intervention. Finally, on the basis of comparison between HBV-positive and HBV-negative pancreatic cancer in more larger clinical specimens, we hope to define pancreatic cancer subtypes, recurrence of disease and response to specific therapies using. These may aid to understand biological characteristics of pancreatic cancer and to develop new drugs for personalized therapy.