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Int J Biol Sci 2013; 9(3):303-312. doi:10.7150/ijbs.6214
Development of a miR-26 Companion Diagnostic Test for Adjuvant Interferon-alpha Therapy in Hepatocellular Carcinoma
1. Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA;
Background & Aims: Adjuvant therapies for hepatocellular carcinoma (HCC) such as interferon-alpha are effective only in a subset of patients. Previously we found that HCC patients with low level of miR-26 have survival benefits from interferon-alpha. The purpose of this study is to develop a standardized miR-26 diagnostic test (referred as MIR26-DX) to assist identification of candidate HCC patients for adjuvant interferon-alpha therapy.
Methods: We developed a multiplex reverse-transcription quantitative polymerase-chain-reaction assay to determine the levels of two HCC-related miR-26 transcripts along with six small RNA reference transcripts. We evaluated archived paraffin-embedded tissues from three cohorts of HCC patients (n=248) who underwent radical resection at three different clinical centers. Fifty-two percent of them underwent adjuvant interferon-alpha therapy. We used Cox-Mantel log-rank test to evaluate patient survival.
Results: We found that the multiplexing assay was stable and reproducible regardless of differences in sample preparations and operators. We developed a matrix template and a scoring algorithm based on a training cohort (n=129) to assign HCC patients, and then applied the template in two test cohorts (n=119). The proportions of HCC patients assigned as low miR-26 by this algorithm were 68, 4, and 63 percent in the training cohort and two test cohorts, respectively. Consistently, HCC with low miR-26 had a favorable response to interferon-alpha with improved median overall survival (≥3year).
Conclusions: MIR26-DX is a simple and reliable companion diagnostic test to select HCC patients for adjuvant interferon-alpha therapy.
Keywords: miR-26, hepatocellular carcinoma, interferon-alpha, adjuvant therapy, companion diagnostics.
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How to cite this article:
Ji J, Yu L, Yu Z, Forgues M, Uenishi T, Kubo S, Wakasa K, Zhou J, Fan J, Tang ZY, Fu S, Zhu H, Jin JG, Sun HC, Wang XW. Development of a miR-26 Companion Diagnostic Test for Adjuvant Interferon-alpha Therapy in Hepatocellular Carcinoma. Int J Biol Sci 2013; 9(3):303-312. doi:10.7150/ijbs.6214. Available from http://www.ijbs.com/v09p0303.htm