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樊嘉课题组以microRNA为目标,取得肝癌早期诊断突破

2011/11/30 来源:生物探索
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11月29日,复旦大学中山医院宣布,该院肝癌研究所樊嘉教授领衔的课题组在肝癌早期诊断方面的研究取得新突破。

中山医院樊嘉教授

中山医院樊嘉教授

11月29日,复旦大学中山医院宣布,该院肝癌研究所樊嘉教授领衔的课题组在肝癌早期诊断方面的研究取得新突破。

我国是肝癌高发国家,全世界50%以上的新发和死亡肝癌患者发生在中国。据介绍,肝癌起病隐匿,超过60%的肝癌患者在初次就诊时已经进入中晚期,从而失去根治性治疗的机会,总体5年生存率只有7%左右。目前临床上常用的肝癌诊断标记物为甲胎蛋白,简称AFP。

然而,AFP诊断肝癌的敏感度和特异度并不十分理想。在妊娠妇女、急慢性肝炎、生殖腺肿瘤和胃肠道肿瘤等人群中AFP亦可能升高。约40%的肝癌患者AFP并不升高,呈AFP阴性。因此,寻找特异性和敏感性均高的诊断肝癌特别是早期肝癌的分子标记物成为目前临床研究的重点和难点。

日前,复旦大学中山医院肝癌研究所科研团队与复旦大学病理系合作,经过三年攻关,终于在肝癌患者血浆中筛选到了由7个microRNA组成的早期肝癌诊断分子标记物。对于小于2cm的肝癌诊断准确率接近90%;效果优于传统的AFP。

樊嘉教授表示,该检测办法方便,只需抽取1毫升血即可在数小时内得出结果,创伤性小,利于连续动态检测和人群的大规模筛查;另外,检测技术要求简便、成本低,易于推广应用。

据悉,该研究成果近日在线发表在国际临床肿瘤领域最权威的学术期刊美国《临床肿瘤学杂志》上(影响因子为18.97),该杂志同期配发了编者按,对该研究成果给予高度评价。

 

Plasma MicroRNA Panel to Diagnose Hepatitis B Virus–Related Hepatocellular Carcinoma

Jian Zhou, Lei Yu, Xue Gao, Jie Hu, Jiping Wang, Zhi Dai, Jie-Fei Wang, Zhiyong Zhang, Shaohua Lu, Xiaowu Huang, Zheng Wang, Shuangjian Qiu, Xiaoying Wang, Guohuan Yang, Huichuan Sun, Zhaoyou Tang, Ying Wu, Hongguang Zhu and Jia Fan

Purpose More than 60% of patients with hepatocellular carcinoma (HCC) do not receive curative therapy as a result of late clinical presentation and diagnosis. We aimed to identify plasma microRNAs for diagnosing hepatitis B virus (HBV) –related HCC.

Patients and Methods Plasma microRNA expression was investigated with three independent cohorts including 934 participants (healthy, chronic hepatitis B, cirrhosis, and HBV-related HCC), recruited between August 2008 and June 2010. First, we used microarray to screen 723 microRNAs in 137 plasma samples for diagnosing HCC. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n = 407) and then validated using an independent cohort (n = 390). Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.

Results We identified a microRNA panel (miR-122, miR-192, miR-21, miR-223, miR-26a, miR-27a and miR-801) that provided a high diagnostic accuracy of HCC (AUC = 0.864 and 0.888 for training and validation data set, respectively). The satisfactory diagnostic performance of the microRNA panel persisted regardless of disease status (AUCs for Barcelona Clinic Liver Cancer stages 0, A, B, and C were 0.888, 0.888, 0.901, and 0.881, respectively). The microRNA panel can also differentiate HCC from healthy (AUC = 0.941), chronic hepatitis B (AUC = 0.842), and cirrhosis (AUC = 0.884), respectively.

Conclusion We found a plasma microRNA panel that has considerable clinical value in diagnosing early-stage HCC. Thus, patients who would have otherwise missed the curative treatment window can benefit from optimal therapy.

文献链接:http://jco.ascopubs.org/content/early/2011/11/16/JCO.2011.38.2697.abstract


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