PLoS ONE (Jan 2012)

Identification of postoperative prognostic microRNA predictors in hepatocellular carcinoma.

  • Ya-Hui Huang,
  • Kwang-Huei Lin,
  • Hua-Chien Chen,
  • Ming-Ling Chang,
  • Chao-Wei Hsu,
  • Ming-Wei Lai,
  • Tse-Ching Chen,
  • Wei-Chen Lee,
  • Yi-Hsin Tseng,
  • Chau-Ting Yeh

DOI
https://doi.org/10.1371/journal.pone.0037188
Journal volume & issue
Vol. 7, no. 5
p. e37188

Abstract

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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.