复旦院士顶级期刊发microRNA癌症研究成果

　　

生物通报道，由复旦大学肝癌研究所所长汤钊猷院士指导的肝癌研究成果文章MicroRNA Expression, Survival, and Response to Interferon in Liver Cancer发表在世界权威期刊《The New England Journal of Medicine》上。该文章发现microRNA-26在乙型肝炎病毒感染相关的肝癌发生中起重要作用，由此揭示了采用干扰素预防肝癌复发的有关机制和敏感患者筛选标志。

 

《The New England Journal of Medicine》同期配发了哈佛大学医学院教授撰写的短评，认为研究不仅从机制上提示炎症介质在肝癌进展中关键性作用，并为提高改善干扰素治疗的效果提出了临床可行的方法。

 

据新华网消息，研究小组发现，在miR-26表达较低的患者接受干扰素治疗后，5年生存率由30%左右提高到65%左右，而miR-26表达较高的患者无论是否接受干扰素治疗，5年生存率相似。

 

由此，医学界找到了miR-26的表达水平这一判断肝癌患者是否适宜接受干扰素治疗的重要筛选指标，并将进一步探索建立快速、简便的检测方法，使之成为临床常规。

 

研究小组还发现，肝癌组织中miR-26表达水平低与IL-6、NF-kB两个炎性因子的表达异常增高有关。IL-6和NF-kB的异常增高在慢性炎症促癌过程中占有重要地位，因此miR-26很可能在乙型肝炎病毒感染相关的肝癌发生中起关键性的作用。

 

参与研究的有孙惠川教授等专家组成的复旦大学附属中山医院课题组与美国国立癌症研究院、香港大学玛丽医院的课题组。据悉，我国在这项研究中享有相关知识产权。

 

 

 

生物通推荐原文检索

MicroRNA Expression, Survival, and Response to Interferon in Liver Cancer

 

Junfang Ji, Ph.D., Jiong Shi, M.D., Anuradha Budhu, Ph.D., Zhipeng Yu, B.S., Marshonna Forgues, B.S., Stephanie Roessler, Ph.D., Stefan Ambs, Ph.D., M.P.H., Yidong Chen, Ph.D., Paul S. Meltzer, M.D., Carlo M. Croce, M.D., Lun-Xiu Qin, M.D., Ph.D., Kwan Man, M.D., Ph.D., Chung-Mau Lo, M.D., Joyce Lee, B.S., Irene O.L. Ng, M.D., Jia Fan, M.D., Ph.D., Zhao-You Tang, M.D., Hui-Chuan Sun, M.D., Ph.D., and Xin Wei Wang, Ph.D.

【Abstract】

Background Hepatocellular carcinoma is a common and aggressive cancer that occurs mainly in men. We examined microRNA expression patterns, survival, and response to interferon alfa in both men and women with the disease.

 

Methods We analyzed three independent cohorts that included a total of 455 patients with hepatocellular carcinoma who had undergone radical tumor resection between 1999 and 2003. MicroRNA-expression profiling was performed in a cohort of 241 patients with hepatocellular carcinoma to identify tumor-related microRNAs and determine their association with survival in men and women. In addition, to validate our findings, we used quantitative reverse-transcriptase–polymerase-chain-reaction assays to measure microRNAs and assess their association with survival and response to therapy with interferon alfa in 214 patients from two independent, prospective, randomized, controlled trials of adjuvant interferon therapy.

 

Results In patients with hepatocellular carcinoma, the expression of miR-26a and miR-26b in nontumor liver tissue was higher in women than in men. Tumors had reduced levels of miR-26 expression, as compared with paired noncancerous tissues, which indicated that the level of miR-26 expression was also associated with hepatocellular carcinoma. Moreover, tumors with reduced miR-26 expression had a distinct transcriptomic pattern, and analyses of gene networks revealed that activation of signaling pathways between nuclear factor B and interleukin-6 might play a role in tumor development. Patients whose tumors had low miR-26 expression had shorter overall survival but a better response to interferon therapy than did patients whose tumors had high expression of the microRNA.

 

Conclusions The expression patterns of microRNAs in liver tissue differ between men and women with hepatocellular carcinoma. The miR-26 expression status of such patients is associated with survival and response to adjuvant therapy with interferon alfa.