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

doi:10.1016/j.humpath.2010.12.010

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

Department of Pathology

Research output: Contribution to journal › Article › peer-review

51 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1391-1400
Number of pages	10
Journal	Human Pathology
Volume	42
Issue number	10
DOIs	https://doi.org/10.1016/j.humpath.2010.12.010
Publication status	Published - 2011 Oct

Bibliographical note

Funding Information:
This work was supported by the Korea Science and Engineering Foundation grant funded by the Korean government (MEST ) (no. R13-2002-044-05001-0 ) and a Student Research Grant ( 10-11 ) from the University of Ulsan College of Medicine, Seoul, Korea.

All Science Journal Classification (ASJC) codes

Pathology and Forensic Medicine

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@article{58687ac790fa475e9d7520fac20ce367,

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.",

author = "Yoon, {Sun Och} and Chun, {Sung Min} and Han, {Eun Hee} and Jene Choi and Jang, {Se Jin} and Koh, {Seung A.} and Shin Hwang and Eunsil Yu",

note = "Funding Information: This work was supported by the Korea Science and Engineering Foundation grant funded by the Korean government (MEST ) (no. R13-2002-044-05001-0 ) and a Student Research Grant ( 10-11 ) from the University of Ulsan College of Medicine, Seoul, Korea. ",

year = "2011",

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doi = "10.1016/j.humpath.2010.12.010",

language = "English",

volume = "42",

pages = "1391--1400",

journal = "Human Pathology",

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publisher = "W.B. Saunders Ltd",

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Deregulated expression of microRNA-221 with the potential for prognostic biomarkers in surgically resected hepatocellular carcinoma. / Yoon, Sun Och; Chun, Sung Min; Han, Eun Hee; Choi, Jene; Jang, Se Jin; Koh, Seung A.; Hwang, Shin; Yu, Eunsil.

In: Human Pathology, Vol. 42, No. 10, 10.2011, p. 1391-1400.

Research output: Contribution to journal › Article › peer-review

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T1 - Deregulated expression of microRNA-221 with the potential for prognostic biomarkers in surgically resected hepatocellular carcinoma

AU - Yoon, Sun Och

AU - Chun, Sung Min

AU - Han, Eun Hee

AU - Choi, Jene

AU - Jang, Se Jin

AU - Koh, Seung A.

AU - Hwang, Shin

AU - Yu, Eunsil

N1 - Funding Information: This work was supported by the Korea Science and Engineering Foundation grant funded by the Korean government (MEST ) (no. R13-2002-044-05001-0 ) and a Student Research Grant ( 10-11 ) from the University of Ulsan College of Medicine, Seoul, Korea.

PY - 2011/10

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N2 - 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.

AB - 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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