Abstract
BackgroundOligonucleotide 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 cases of hepatocellular carcinoma (HCC) and to evaluate the correlation between CNAs and clinicopathologic findings.MethodsaCGH was performed on 75 HCC cases with paired DNA samples from tumor and adjacent nontumor tissues. Survival outcomes from these cases were analyzed based on Barcelona-Clinic Liver Cancer Stage (BCLC), Edmondson-Steiner grade (E-S), and recurrence status. Correlation of CNAs with clinicopathologic findings was analyzed by Wilcoxon rank test and clustering vs. K means.ResultsThe 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.ConclusionsThese 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.
Highlights
Oligonucleotide array comparative genomic hybridization analysis has been used for detecting somatic copy number alterations (CNAs) in various types of tumors
A relative frequency for each smallest overlap regions (SORs) was calculated by the number of cases with overlapped CNAs divided by the number of all cases
These results indicated that the Barcelona-Clinic Liver Cancer Stage (BCLC) stages and recurrence status could be an independent predictor for prognosis and E-S grades might be a modifying predictor affected by stage and recurrence
Summary
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 cases of hepatocellular carcinoma (HCC) and to evaluate the correlation between CNAs and clinicopathologic findings. Recurrent CNAs correlating with stages and prognosis of HCC [12,13,14,15,16] and associating with infections by Hepatitis B or C virus [17, 18] have been reported. Genomic profiles and clusters of CNAs for all cases and cases with different clinicopathologic findings were compared to evaluate correlations of CNAs with tumor stages, grades and recurrence.
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