Correlating genomic copy number alterations with clinicopathologic findings in a case series of hepatocellular carcinoma

Abstract

Background: Oligonucleotide array comparative genomic hybridization (aCGH) analysis has been used for detecting somatic copy number alterations (CNAs) in various types of tumors. This study aimed to assess the clinical utility of aCGH for a case series of hepatocellular carcinoma (HCC) and to evaluate the correlation between CNAs and clinicopathologic findings.Methods: Survival outcomes from this case series were analyzed based on Barcelona-Clinic Liver Cancer Stage (BCLC), Edmondson-Steiner grade (E-S), and recurrence status. aCGH was performed on 75 HCC cases with paired DNA samples from tumor and adjacent nontumor tissues. Correlation of CNAs with clinicopathologic findings was analyzed by Wilcoxon rank test and clustering vs. K means.Results: The survival outcomes indicated that BCLC stages and recurrence status could be predictors and E-S grades could be a modifier for HCC. The most common CNAs involved gains of 1q and 8q and a loss of 16q (50%), losses of 4q and 17p and a gain of 5p (40%), and losses of 8p and 13q (30%). Analyses of genomic profiles and clusters identified that losses of 4q13.2q35.2 and 10q22.3q26.13 seen in cases of stage A, grade III and nonrecurrence were likely correlated with good survival, while loss of 1p36.31p22.1 and gains of 2q11.2q21.2 and 20p13p11.1 seen in cases of stage C, grade III and recurrence were possibly correlated with worst prognosis. Conclusions: These results indicated that aCGH analysis could be used to detect recurrent CNAs and involved key genes and pathways in patients with HCC. Further analysis on a large case series to validate the correlation of CNAs with clinicopathologic findings of HCC could provide information to interpret CNAs and predict prognosis.