Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2017; 23(44): 7818-7829
Published online Nov 28, 2017. doi: 10.3748/wjg.v23.i44.7818
Prediction of early-stage hepatocellular carcinoma using OncoScan chromosomal copy number aberration data
Ming-Chin Yu, Chao-Wei Lee, Yun-Shien Lee, Jang-Hau Lian, Chia-Lung Tsai, Yi-Ping Liu, Chun-Hsing Wu, Chi-Neu Tsai
Ming-Chin Yu, Chao-Wei Lee, Yi-Ping Liu, Chun-Hsing Wu, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Ming-Chin Yu, Department of Surgery, Xiamen Chang Gung Hospital, Xiamen 361028, China
Chao-Wei Lee, Chi-Neu Tsai, Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan 33302, Taiwan
Yun-Shien Lee, Jang-Hau Lian, Chia-Lung Tsai, Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Yun-Shien Lee, Department of Biotechnology, Ming-Chuan University, Taoyuan 33348, Taiwan
Chi-Neu Tsai, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Author contributions: Yu MC and Tsai CN designed the research; Lian JH, Liu YP and Wu CH performed the research; Lee YS, Lian JH and Tsai CL contributed to the analysis; Yu MC and Lee CW analyzed the clinical data; Yu MC and Tsai CN wrote the paper.
Supported by the Chang Gung Memorial Hospital in Taiwan, No. CMRPG 3C0951-3 and No. CMRPG 3A0671 to Yu MC, and No. CMRPD3F0011 to Tsai CN.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the Chang Gung Memorial Hospital in Linkou, Taiwan (#104-3511C).
Conflict-of-interest statement: All authors declare no conflict of interest.
Data sharing statement: Clinical dataset available from Dr. Yu MC at mingchin2000@gmail.com.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Chi-Neu Tsai, PhD, Graduate Institute of Clinical Medical Sciences, Chang Gung University, 259 Wen-Hwa 1st Rd, Guishan Dist., Taoyuan 33302, Taiwan. pink7@mail.cgu.edu.tw
Telephone: +886-3-2118800-3480 Fax: +886-3-3280170
Received: September 19, 2017
Peer-review started: September 20, 2017
First decision: October 11, 2017
Revised: October 26, 2017
Accepted: November 7, 2017
Article in press: November 7, 2017
Published online: November 28, 2017
Processing time: 69 Days and 0.3 Hours
ARTICLE HIGHLIGHTS
Research background

Most patients with early-stage (stageI/II) hepatocellular carcinoma (HCC) have a favorable outcome; nevertheless, increased genomic instability possibly leads to postoperative recurrence.

Research motivation

Previous studies using frozen HCC tumor tissue with array comparative genomic hybridization were of limited clinical value because of the absence of patient survival data. Since formalin fixed, paraffin-embedded (FFPE) samples are the largest bio-resource with long-term patient survival data found in every hospital worldwide, the aim of this research was to determine whether FFPE specimens of early-stage HCC with long-term survival data may be used with OncoScan GeneChips towards prognostic analysis of patients.

Research objectives

The study enrolled 120 patients with early-stage HCC and ten nonmalignant liver tumors or normal HCC counterpart tissues to explore genome instability and copy number aberrations (CNAs) in early-stage HCC.

Research methods

Extracted DNA was processed at the Genomic Medicine Core Laboratory and analyzed with the Affymetrix OncoScan platform to assess CNAs and loss of heterozygosity (LOH). We reliably obtained global genome amplification/deletion and overall percentage genome change from all FFPE samples in our cohort.

Research results

CNA amplifications were clustered at chromosomes 1q21.1-q44 and 8q12.3-24.3 and deletions at 4q13.1-q35.2, 8p 23.2-21.1, 16q23.3-24.3, and 17p13.3-12 in patients with early-stage HCC. We found that percentage of genome change ≥ 60% was an independent factor for worse prognosis and MYC, ELAC2, and SYK (amplification) as well as GAK, MECOM, and WRN (deletion) were the most powerful predicting genes. Using Asian patients with stage I HCC from The Cancer Genome Atlas as an independent cohort, we found that patients harboring CNAs affecting these genes were also predicted to have poorer outcomes.

Research conclusions

The identification of percent genome change and six independently predictive genes from the Affymetrix OncoScan platform illustrates that chromosomal alterations are crucial for outcome of patients with early-stage HCC after resection, which may be further applied for clinical practice using OncoScan or a custom-designed chip covering these six genes regions.

Research perspectives

Genome instability was related to early-stage HCC clinical outcome and patients with CNAs affecting MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection. In the era of precision medicine, the identification of CNAs in these six genes could be further applied for clinical practice using a small custom-designed chip.