复旦大学附属中山医院的肝癌研究再次取得突破性进展，10月15日发布已发现人体内microRNA miR-26在乙型肝炎病毒感染相关的肝癌发生中起较为关键的作用，miR-26表达水平低的人最有可能采用干扰素预防肝癌复发的可能机制，从而降低复发，延长生存。据介绍，该项肝癌研究成果10月8日发表在《新英格兰医学杂志》（NEJM），获得国际医学界认可。中山医院将很快运用成果对病人开展筛查，给肝癌患者带来延长生存福音。
肝癌是影响我国人口的主要癌症杀手之一，目前，全世界每年新增60万肝癌患者，其中中国占了大部分。手术切除是肝癌患者获得长期生存的主要手段。但是肝癌术后的复发率高达40-60%，是影响患者生存的最主要原因。因此，如何减少术后复发是肝癌临床面临的重大课题，也是复旦大学肝癌研究所的主要科研方向。
在中国工程院院士、复旦大学附属中山医院肝癌研究所所长汤钊猷教授指导下，由孙惠川教授等专家组成的中山医院课题组与美国国立癌症研究院、香港大学玛丽医院密切合作，历时三年半科技攻关，发现microRNA miR-26在乙型肝炎病毒感染相关的肝癌发生中起较为关键的作用，肝癌患者中该遗传密码表达水平低的人最有可能采用干扰素预防肝癌复发，从而找到了可能降低复发机制，延长肝癌患者生存。
复旦大学肝癌研究所研究最早发现干扰素可以显著抑制肝癌的生长、转移和切除以后的复发，之后的临床研究也证实干扰素治疗可以减少肝癌术后的复发。由于人体的复杂性，干扰素不可能在所有患者身上都能显示良好的效果，进一步提高疗效的关键在于寻找对干扰素治疗的敏感患者的特征。研究发现，肝癌组织中miR-26表达水平较低与IL-6、NF-kB的表达异常增高有关。医学已证实，IL-6和NF-kB的异常增高在慢性炎症促癌中占有重要地位，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较为关键的作用。
孙惠川教授等专家组的研究进一步发现在miR-26表达较低的患者接受干扰素治疗后，其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，其5年生存率相似。由于干扰素具有调节免疫功能，miR-26的表达可成为肝癌患者是否接受干扰素治疗的筛选指标。（生物谷Bioon.com）
生物谷专题：RNAi miRNA
生物谷推荐原始出处：
NEJM Volume 361:1437-1447 October 8, 2009
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.
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.
