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Deregulated expression of microRNA-221 with the potential for prognostic biomarkers in surgically resected hepatocellular carcinoma

 Sun Och Yoon  ;  Sung-Min Chun  ;  Eun Hee Han  ;  Jene Choi  ;  Se Jin Jang  ;  Seung A Koh  ;  Shin Hwang  ;  Eunsil Yu 
 HUMAN PATHOLOGY, Vol.42(10) : 1391-1400, 2011 
Journal Title
Issue Date
Adult ; Aged ; Biomarkers, Tumor/biosynthesis* ; Carcinoma,Hepatocellular/diagnosis ; Carcinoma,Hepatocellular/metabolism* ; Carcinoma,Hepatocellular/surgery ; Female ; Humans ; Liver/metabolism ; Liver/surgery ; Liver Neoplasms/diagnosis ; Liver Neoplasms/metabolism* ; Liver Neoplasms/surgery ; Male ; MicroRNAs/biosynthesis* ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/diagnosis ; Neoplasm Recurrence, Local/metabolism ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Up-Regulation
Microrna ; Hepatocellular carcinoma ; RT-PCR ; Formalin-fixed, paraffin-embedded tissue
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.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
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