Identification of postoperative prognostic microRNA predictors in hepatocellular carcinoma.
Comparison of microRNA (miRNA) expression profiles in the noncancerous liver tissues adjacent to hepatocelluar carcinomas (HCCs) was a strategy to identify postoperative prognostic predictors in this study. Expression profiles of 270 miRNAs were determined in the paraneoplastic liver tissues of 12 HCC patients with known postoperative prognosis. A panel of candidate miRNA predictors was identified. The prognostic predictive value of these candidate miRNAs was then verified in 216 postoperative HCC patients. Univariate analysis identified 8 and 3 miRNA predictors for recurrence-free (RFS) and overall (OS) survivals, respectively. Multivariate analysis revealed high expression levels of miR-155 (HR, 2.002 [1.324-3.027]; P = .001), miR-15a (HR, 0.478 [0.248-0.920]; P = .027), miR-432 (HR, 1.816 [1.203-2.740]; P = .015), miR-486-3p (HR, 0.543 [0.330-0.893]; P = .016), miR-15b (HR, 1.074 [1.002-1.152]; P = .043) and miR-30b (HR, 1.102 [1.025-1.185]; P = .009) were significantly associated with RFS. When clinicopathological predictors were included, multivariate analysis revealed that tumor number and miR-432, miR-486-3p, and miR-30b expression levels remained significant as independent predictors for RFS. Additionally, expression knockdown of miR-155 in J7 and Mahlavu hepatoma cells resulted in decreased cell growth and enhanced cell death in xenograft tumors, suggesting an oncogenic effect of miR-155. In conclusion, significant prognostic miRNA predictors were identified through examination of miRNA expression levels in paraneoplastic liver tissues. Functional analysis of a miRNA predictor, miR-155, suggested that the prognostic miRNA predictors identified under this strategy could serve as potential molecular targets for anticancer therapy.
Department of Hepato-Gastroenterology, Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Ya-Hui
YH
Huang
Kwang-Huei
KH
Lin
Hua-Chien
HC
Chen
Ming-Ling
ML
Chang
Chao-Wei
CW
Hsu
Ming-Wei
MW
Lai
Tse-Ching
TC
Chen
Wei-Chen
WC
Lee
Yi-Hsin
YH
Tseng
Chau-Ting
CT
Yeh
D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis
D035683:MicroRNAs