来自第四军医大学肿瘤生物学国家重点实验室的研究人员发现了我国首个新型通用癌生物标志物：HAb18G/CD147，这一标志物作为癌症的全新药靶，对临床诊断和预后判断具有重要意义。这一研究成果公布在《致癌基因》（Oncogene），《生物科学与生物工程期刊》（J Biosci Bioeng.）等杂志上。
领导这一研究的是第四军医大学陈志南院士，陈志南院士在肿瘤转移相关分子相互作用的分子调控网络研究、粘附分子HAb18G/CD147与整合素家族及AnnexinⅡ相互作用参与肝癌细胞的侵袭转移、HAb18G/CD147分子通过调节EMT现象参与肿瘤发生、HAb18G/CD147剪接异构体与结构生物学研究、癌基因组与个体化医学研究、细胞周期与肿瘤生物学等相关基础及应用基础研究方面取得重要进展。
据报道，为了能探讨综合治疗癌症的新方法，陈志南院士研究组开拓思路，高起点地选择了肝癌单抗药靶分子的研究及抗炎、抗病毒功能、肝癌移植抗复发治疗等多层面的研究，经反复检测实验，他们终于成功研制出HAb18G/CD147拮抗剂（利卡汀）。经对各类癌组织的28组组织芯片、1252个样品点、1117例乳腺癌病理标本进行组织学和血清学检测，结果显示：HAb18G/CD147对良性瘤不表达，对癌表达率为66.6%，能使肝癌移植治疗一年复发率降低30.4%，患者生存率提高24.7%，这表明HAb18G/CD147是一个新型通用、有较好特异性、与癌症发生发展密切相关的标志物，为癌症的早期预警、病理分型、分期诊断、预后判断有着重要的应用价值。
研究还发现，HAb18G/CD147对抗类风湿关节炎（RA）、SARS、HIV-1等病毒性疾病，具有良好的抗炎、抑制作用，是一个新型稳定的治疗药靶。在此基础上，他们研发出具有我国自主知识产权的HAb18G/CD147癌症标志物免疫组化诊断试剂盒，并获得PCT国际专利授权1项和国家颁发的知识产权专利证书及生产许可证书。目前这一试剂盒已投入批量生产。
这项研究由于涉及相关产业，因此引发了争议，据羊城晚报报道，媒体报道的HAb18G/CD147癌症标志物免疫组化诊断试剂盒，不涉及公司和第四军医大学关于《碘【131I】-HAb18肝癌单克隆抗体注射液技术转让合同书》的技术转让范畴。目前公司产品利卡汀仅用于治疗原发性肝癌，其对公司业绩暂难评估。（生物谷Bioon.com）
生物谷推荐原文出处：
Oncogene DOI： 10.1038/onc.2011.149
HAb18G/CD147 promotes epithelial-mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug.
Wu J,Ru N-Y NY,Zhang Y,Li Y,Wei D,Ren Z,Huang XF,Chen ZN,Bian H
Epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β (TGF-β) is implicated in hepatocarcinogenesis and hepatocellular carcinoma (HCC) metastasis. HAb18G/CD147, which belongs to the CD147 family, is an HCC-associated antigen that has a crucial role in tumor invasion and metastasis. The goal of this study was to investigate the role of HAb18G/CD147 during EMT in hepatocarcinogenesis. Human normal hepatic cell lines QZG and L02, primary mouse hepatocytes and nude mouse models were used to determine the role of HAb18G/CD147 in EMT, and the involvement of the TGF-β-driven pathway. A dual-luciferase reporter assay and ChIP were used to investigate the transcriptional regulation of the CD147 gene. Samples from patients with liver disease were assessed to determine the relationship between HAb18G/CD147 and typical markers for EMT. Our results show that upregulation of HAb18G/CD147 is induced by TGF-β coupled with downregulation of E-cadherin and upregulation of N-cadherin and vimentin. The expression of HAb18G/CD147 is controlled by the cell survival PI3K/Akt/GSK3β signaling pathway, and is directly regulated by the transcription factor Slug. Transfection of CD147 also induces an elevated expression of TGF-β. CD147-transfected hepatocytes have mesenchymal phenotypes that accelerate tumor formation and tumor metastasis in vivo. Immunohistochemistry analysis shows a negative correlation between HAb18G/CD147 and E-cadherin expression (r(s)=-0.3622, P=0.0105), and a positive correlation between HAb18G/CD147 and Slug expression (r(s)=0.3064, P=0.0323) in human HCC tissues. Our study uncovers a novel role of HAb18G/CD147 in mediating EMT in the process of HCC progression and showed that CD147 is a Slug target gene in the signaling cascade TGF-β→PI3K/Akt→GSK3β→Snail→Slug→CD147. Our results suggest that CD147 may be a potential target for the treatment and prevention of HCC.
