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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2013 > Volume 9 Number 3 > Junfang Ji1,✉, Lei Yu1,2, Zhipeng Yu1, Marshonna Forgues1, Takahiro Uenishi3, Shoji Kubo3, Kenichi Wakasa3, Jian Zhou2, Jia Fan2, Zhao-You Tang2, Shijun Fu4, Hongguang Zhu4, Jason Gang Jin4, Hui-Chuan Sun2, Xin Wei Wang1,✉

Development of a miR-26 Companion Diagnostic Test for Adjuvant Interferon-alpha Therapy in Hepatocellular Carcinoma

Junfang Ji1,✉, Lei Yu1,2, Zhipeng Yu1, Marshonna Forgues1, Takahiro Uenishi3, Shoji Kubo3, Kenichi Wakasa3, Jian Zhou2, Jia Fan2, Zhao-You Tang2, Shijun Fu4, Hongguang Zhu4, Jason Gang Jin4, Hui-Chuan Sun2, Xin Wei Wang1,✉
1. Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; 2. Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China; 3. Department of Hepato-Biliary-Pancreatic Surgery (U.T., K.S.) and Department of Diagnostic Pathology (W.K.), Osaka City University Graduate School of Medicine, Osaka, Japan; 4. ShanghaiBio Corporation, Shanghai, China & North Brunswick, New Jersey, USA.
Abstract :

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

Date Deposited : 09 Apr 2015 15:41

Last Modified : 09 Apr 2015 15:41

Official URL: http://www.ijbs.com/ms/archive

Volume 9, Number 3, - 2013 , ISSN 1545-1003

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