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Previous Volume 361:1437-1447 October 8, 2009 Number 15 Next

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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.

Source Information

From the Liver Carcinogenesis Section (J.J., J.S., A.B., Z.Y., M.F., S.R., X.W.W.), Breast and Prostate Unit, Laboratory of Human Carcinogenesis (S.A.), and Genetics Branch (Y.C., P.S.M.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; the Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China (J.S., L.-X.Q., J.F., Z.-Y.T., H.-C.S.); the Comprehensive Cancer Center, Ohio State University, Columbus (C.M.C.); and the Departments of Surgery (K.M., C.-M.L.) and Pathology (J.L., I.O.L.N.), Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.

Address reprint requests to Dr. Wang at the National Cancer Institute, 37 Convent Dr., Bldg. 37, Rm. 3044A, Bethesda, MD 20892, or at xw3u{at}nih.gov; or to Dr. Sun at the Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China, or at sun.huichuan{at}zs-hospital.sh.cn.

Full Text of this Article

This article has been cited by other articles:

• (2009). MicroRNA Expression in Hepatocellular Cancer. JWatch Oncology and Hematology 2009: 2-2 [Full Text]  
• Lieberman, J. (2009). Micromanaging Cancer. NEJM 361: 1500-1501 [Full Text]