摘要
Aim:Deregulation of microRNAs(miRNAs)expression has been identified in hepatocellular carcinoma(HCC),but few results are consistent.The objective of this study is to investigate“HCC tumor type specific”and“tumor common”miRNA panels.Methods:The authors integrate and analyze clinical,etiologic and miRNA profiles data from 9 types of solid tumors in The Cancer Genome Atlas(TCGA)and HCC data from Columbia University Medical Center(CUMC).Results:Levels of 33 miRNAs were significant different between HCC tumor and paired non-tumor tissues(over 2-fold changes)after Bonferroni correction for multiple comparisons,and most(28 miRNAs)were down-regulated in HCC tumors.Using this panel,the authors well classified HCC tumor tissues with 4 misclassifications among 48 paired tissues.Validating this panel in an additional 302 HCC tumor tissues,the authors almost perfectly distinguished tumor from non-tumor tissues with only two misclassifications(99%of HCC tissues correctly classified).Evaluating miRNA profiles in 32 independent HCC paired tissues from CUMC,the authors observed 40 miRNAs significantly deregulated in HCC with over 2-fold changes;14 overlapped with those identified in TCGA.Subgroup analyses by HCC etiology found that 4 upregulated and 8 downregulated miRNAs were significantly associated with alcohol-related HCC.There were 7 and 4 miRNAs significantly associated with hepatitis B virus-and hepatitis C virus-related HCC,respectively.Data for the first time revealed that miR-24-1,miR-130a and miR-505 were significantly down-regulated only in HCC tumors;miR-142 and miR-455 were significantly down-regulated in HCC,but up-regulated in 5 other solid tumors;suggesting their HCC“tumor type specific”characteristics.A panel of 8 miRNAs was significant in at least 5 tumor types,including HCC,and was identified as“tumor common”marker.Conclusion:The authors concluded that aberrant miRNA panels have HCC“tumor type specificity”and may be affected by etiologic factors.
基金
supported by NIH grants R01 ES005116,P30 ES009089,P30 CA013696,R03 CA156629。
