復旦大學附屬中山醫(yī)院的肝癌研究再次取得突破性進展，10月15日發(fā)布已發(fā)現(xiàn)人體內(nèi)microRNA miR-26在乙型肝炎病毒感染相關(guān)的肝癌發(fā)生中起較為關(guān)鍵的作用,，miR-26表達水平低的人最有可能采用干擾素預(yù)防肝癌復發(fā)的可能機制,，從而降低復發(fā),，延長生存,。據(jù)介紹,，該項肝癌研究成果10月8日發(fā)表在《新英格蘭醫(yī)學雜志》（NEJM）,，獲得國際醫(yī)學界認可。中山醫(yī)院將很快運用成果對病人開展篩查,，給肝癌患者帶來延長生存福音,。
肝癌是影響我國人口的主要癌癥殺手之一，目前,，全世界每年新增60萬肝癌患者,，其中中國占了大部分。手術(shù)切除是肝癌患者獲得長期生存的主要手段,。但是肝癌術(shù)后的復發(fā)率高達40-60%,，是影響患者生存的最主要原因。因此,，如何減少術(shù)后復發(fā)是肝癌臨床面臨的重大課題,，也是復旦大學肝癌研究所的主要科研方向。
在中國工程院院士,、復旦大學附屬中山醫(yī)院肝癌研究所所長湯釗猷教授指導下,，由孫惠川教授等專家組成的中山醫(yī)院課題組與美國國立癌癥研究院、香港大學瑪麗醫(yī)院密切合作,，歷時三年半科技攻關(guān),，發(fā)現(xiàn)microRNA miR-26在乙型肝炎病毒感染相關(guān)的肝癌發(fā)生中起較為關(guān)鍵的作用，肝癌患者中該遺傳密碼表達水平低的人最有可能采用干擾素預(yù)防肝癌復發(fā),，從而找到了可能降低復發(fā)機制,，延長肝癌患者生存。
復旦大學肝癌研究所研究最早發(fā)現(xiàn)干擾素可以顯著抑制肝癌的生長,、轉(zhuǎn)移和切除以后的復發(fā),，之后的臨床研究也證實干擾素治療可以減少肝癌術(shù)后的復發(fā)。由于人體的復雜性,，干擾素不可能在所有患者身上都能顯示良好的效果，進一步提高療效的關(guān)鍵在于尋找對干擾素治療的敏感患者的特征,。研究發(fā)現(xiàn),，肝癌組織中miR-26表達水平較低與IL-6、NF-kB的表達異常增高有關(guān),。醫(yī)學已證實,，IL-6和NF-kB的異常增高在慢性炎癥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關(guān)的肝癌發(fā)生中起較為關(guān)鍵的作用,。
孫惠川教授等專家組的研究進一步發(fā)現(xiàn)在miR-26表達較低的患者接受干擾素治療后,，其5年生存率由30%左右提高到65%左右，而miR-26表達較高的患者無論是否接受干擾素治療,，其5年生存率相似,。由于干擾素具有調(diào)節(jié)免疫功能,，miR-26的表達可成為肝癌患者是否接受干擾素治療的篩選指標。（生物谷Bioon.com）
生物谷專題：RNAi miRNA
生物谷推薦原始出處：
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.
