한빛사논문, 상위피인용논문
- 조회2,933
Abstract
Haeryoung Kim1, Gi Hong Choi2, Deuk Chae Na3, Ei Young Ahn3, Gwang Il Kim3, Jae Eun Lee3, Jai Young Cho4, Jeong Eun Yoo3, Jin Sub Choi2, Young Nyun Park3,5,6,*,‡
1Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
2Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
3Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
4Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
5Center for Chronic Metabolic Disease, Brain Korea 21 Project for Medical Science, University College of Medicine, Seoul, Korea
6Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea
*Correspondence: Young Nyun Park, Department of Pathology and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul, 120-752, Korea
Keywords:keratin 19;epithelial-mesenchymal transition;tissue microarray;survival
Abstract
There is a recently proposed subtype of hepatocellular carcinoma (HCC) which is histologically similar to usual HCC but characterized by the expression of “stemness”-related markers. A large-scale study on two different cohorts of HCCs was performed, to investigate the clinicopathologic features and epithelial-mesenchymal transition (EMT)-related protein expression status of this subtype of HCCs. The expression status of “stemness”-related (K19, CD133, EpCAM and c-kit) and EMT-related markers (snail, S100A4, uPAR, ezrin, vimentin, E-cadherin, MMP2) were examined using tissue microarrays from cohort 1 HCCs (n=137). K19 protein expression in cohort 2 HCCs (n=237) was correlated with the clinicopathologic parameters and mRNA levels of K19, uPAR, VIL2, Snail, Slug and Twist. K19, EpCAM, c-kit and CD133-positivity were seen in 18.2%, 35.0%, 34.3% and 24.8%, respectively. K19 was most frequently expressed in combination with at least one other “stemness”-related marker (92.0%). K19-positive HCCs demonstrated more frequent major vessel invasion, and increased tumor size compared to K19-negative HCCs (p<0.05). K19 was most significantly associated with EMT-related protein expression (vimentin, S100A4, uPAR, ezrin) (p<0.05) and a poor prognosis (overall survival: p=0.018, disease-free survival: p=0.007) in cohort 1. In cohort 2, HCCs with high K19 mRNA levels demonstrated higher mRNA levels of Snail, uPAR and MMP2 (p<0.05). K19-positive HCCs demonstrated more frequent microvascular invasion, fibrous stroma, and less tumor capsule formation compared to K19-negative HCCs (p<0.05). K19 expression was a significant independent predictive factor of poor disease-free survival (p=0.032).
Conclusion:
K19 was well-correlated with clinicopathologic features of tumor aggressiveness compared to other “stemness”-related proteins. K19-positive HCCs showed significantly increased EMT-related protein and mRNA expression, suggesting they may acquire more invasive characteristics compared to K19-negative HCCs through the up-regulation of EMT-associated genes. (HEPATOLOGY 2011.)
논문정보
- Research article
- 2011년 07월 (BRIC 등록일 )
- 국내 연구진
- 의약학 > 종양의학
- 120회 이상 인용된 논문 (상위피인용논문 등록일 2020-07-15)
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