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Identification of Postoperative Prognostic MicroRNA Predictors in Hepatocellular Carcinoma

Author

Listed:
  • 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

Abstract

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.

Suggested Citation

  • 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, 2012. "Identification of Postoperative Prognostic MicroRNA Predictors in Hepatocellular Carcinoma," PLOS ONE, Public Library of Science, vol. 7(5), pages 1-10, May.
    • Handle: RePEc:plo:pone00:0037188
    DOI: 10.1371/journal.pone.0037188
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    1. Jun Lu & Gad Getz & Eric A. Miska & Ezequiel Alvarez-Saavedra & Justin Lamb & David Peck & Alejandro Sweet-Cordero & Benjamin L. Ebert & Raymond H. Mak & Adolfo A. Ferrando & James R. Downing & Tyler , 2005. "MicroRNA expression profiles classify human cancers," Nature, Nature, vol. 435(7043), pages 834-838, June.
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