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
Abstract
AIM

To identify chromosomal copy number aberrations (CNAs) in early-stage hepatocellular carcinoma (HCC) and analyze whether they are correlated with patient prognosis.

METHODS

One hundred and twenty patients with early-stage HCC were enrolled in our study, with the collection of formalin fixed, paraffin-embedded (FFPE) specimens and clinicopathological data. Tumor areas were marked by certified pathologists on a hematoxylin and eosin-stained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix OncoScan platform to assess CNAs and loss of heterozygosity (LOH). Ten individuals with nonmalignant disease were used as the control group. Another cohort consisting of 40 patients with stage I/II HCC were enrolled to analyze gene expression and to correlate findings with the OncoScan data.

RESULTS

Copy number amplifications occurred at chromosomes 1q21.1-q44 and 8q12.3-24.3 and deletions were found at 4q13.1-q35.2, 8p 23.2-21.1, 16q23.3-24.3, and 17p13.3-12, while LOH commonly occurred at 1p32.3, 3p21.31, 8p23.2-21.1, 16q22.1-24.3, and 17p 13.3-11 in early-stage HCC. Using Cox regression analysis, we also found that a higher percentage of genome change (≥ 60%) was an independent factor for worse prognosis in early-stage HCC (P = 0.031). Among the 875 genes in the OncoScan GeneChip, six were independent predictors of worse disease-free survival, of which three were amplified (MYC, ELAC2, and SYK) and three were deleted (GAK, MECOM, and WRN). Further, patients with HCC who exhibited ≥ 3 CNAs involving these six genes have worse outcomes compared to those who had < 3 CNAs (P < 0.001). Similarly, Asian patients with stage I HCC from The Cancer Genome Atlas harboring CNAs with these genes were also predicted to have poorer outcomes.

CONCLUSION

Patients with early-stage HCC and increased genome change or CNAs involving MYC, ELAC2, SYK, GAK, MECOM, or WRN are at risk for poorer outcome after resection.

Keywords: Early-stage hepatocellular carcinoma, Copy number aberration, Prognosis, OncoScan, Molecular inversion probe

Core tip: In this paper, we report that patients with early-stage hepatocellular carcinoma presenting a higher percentage of genome change or copy number aberrations affecting MYC, ELAC2, SYK, GAK, MECOM, or WRN are predicted to have worse outcomes, and they should be intensively followed after resection.