International Journal of Biological Sciences

Impact factor
3.873

ISSN 1449-2288

News feeds of IJBS published articles
My Manuscript
My Account

Journal of Biomedicinenew

Theranostics

International Journal of Medical Sciences

Journal of Cancer

Oncomedicine

Journal of Genomics

Journal of Bone and Joint Infection (JBJI)

Nanotheranostics

Journal of Genomics now in PubMed/PubMed Central. Submit manuscript...

PubMed Central Indexed in Journal Impact Factor

Int J Biol Sci 2013; 9(3):303-312. doi:10.7150/ijbs.6214

Research Paper

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.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
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