title: Deregulated expression of microRNA-221 with the potential for prognostic biomarkers in surgically resected hepatocellular carcinoma.
abstract: Aberrant expression of specific microRNAs in hepatocellular carcinomas has recently been reported. We examined expression patterns of 4 microRNAs (microRNA-221, microRNA-222, microRNA-21, and microRNA-155) to evaluate their potential as relevant biomarkers by quantitative real-time reverse transcriptase-polymerase chain reaction using formalin-fixed, paraffin-embedded tissues of 115 surgically resected hepatocellular carcinoma and paired nonneoplastic liver cases as well as 21 normal liver samples from cancer-free individuals. MicroRNA-221, microRNA-222, and microRNA-21 were differentially overexpressed in hepatocellular carcinoma compared with nonneoplastic and normal livers (P < .001). The mean fold changes in microRNA-221, microRNA-222, and microRNA-21(hepatocellular carcinoma to matched nonneoplastic liver) were 4.00, 4.44, and, 3.67, respectively. In addition, nonneoplastic liver tissues displayed higher levels of microRNA-221, microRNA-222, microRNA-21, and microRNA-155 than normal livers (P < .001, respectively). However, the overexpression of the 4 microRNAs showed no consistent relevance to the known prognostic clinicopathologic parameters. High expression of microRNA-221 in hepatocellular carcinomas was significantly related to shorter time to local recurrence (P < .001) and determined as an independent predictor for local recurrence (P = .001). The fold changes in microRNA-221 (hepatocellular carcinoma to matched nonneoplastic liver) less than 1 were more commonly detected in cases of distant metastases than those of disease-free and local recurrence (P = .009). The fold changes less than 1 were related to reduced metastasis-free survival (P = .006) and thus can be used as an independent predictor of distant metastasis after surgical resection (P = .027). Based on these results, we propose the possible role of microRNA-221, microRNA-222, microRNA-21, and microRNA-155 dysregulation in hepatocarcinogenesis and the potential of microRNA-221 dysregulation for predicting local recurrence and distant metastasis after curative surgery.
authors: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors: Sun Och
authors: SO
authors: Yoon
authors: Sung-Min
authors: SM
authors: Chun
authors: Eun Hee
authors: EH
authors: Han
authors: Jene
authors: J
authors: Choi
authors: Se Jin
authors: SJ
authors: Jang
authors: Seung A
authors: SA
authors: Koh
authors: Shin
authors: S
authors: Hwang
authors: Eunsil
authors: E
authors: Yu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000601:surgery; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C524942:MIRN155 microRNA, human; C524940:MIRN21 microRNA, human; C525709:MIR221, human; C525710:MIR222, human