MicroRNA expression, survival, and response to interferon in liver cancer

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

Research output: Contribution to journalArticlepeer-review

669 Scopus citations

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 κB 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.

Original languageEnglish (US)
Pages (from-to)1437-1447
Number of pages11
JournalNew England Journal of Medicine
Volume361
Issue number15
DOIs
StatePublished - Oct 8 2009

ASJC Scopus subject areas

  • Medicine(all)

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