Prediction of early-stage hepatocellular carcinoma using Onco Scan chromosomal copy number aberration data

作     者：Ming-Chin Yu Chao-Wei Lee Yun-Shien Lee Jang-Hau Lian Chia-Lung Tsai Yi-Ping Liu Chun-Hsing Wu Chi-Neu Tsai 

作者机构：Department of SurgeryChang Gung Memorial Hospital Department of SurgeryXiamen Chang Gung Hospital Graduate Institute of Clinical Medical SciencesChang Gung University Genomic Medicine Core LaboratoryChang Gung Memorial Hospital Department of BiotechnologyMing-Chuan University Department of PediatricsChang Gung Memorial Hospital 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2017年第23卷第44期

页      面：7818-7829页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：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 

主　　题：Early-stage hepatocellular carcinoma Copy number aberration Prognosis Onco Scan Molecular inversion probe 

摘      要：AIM To identify chromosomal copy number aberrations(CNAs) in early-stage hepatocellular carcinoma(HCC) and analyze whether they are correlated with patient *** 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 eosinstained slide, and cancer and adjacent non-cancerous tissues underwent extraction of DNA, which was analyzed with the Affymetrix Onco Scan 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 Onco Scan *** Copy number amplifications occurred at chromosomes 1 q21.1-q44 and 8 q12.3-24.3 and deletions were found at 4 q13.1-q35.2, 8 p 23.2-21.1, 16 q23.3-24.3, and 17 p13.3-12, while LOH commonly occurred at 1 p32.3, 3 p21.31, 8 p23.2-21.1, 16 q22.1-24.3, and 17 p 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 Onco Scan Gene Chip, 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 *** 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.