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Increased expression of stemness markers and altered tumor stroma in hepatocellular carcinoma under TACE-induced hypoxia: A biopsy and resection matched study

 Ji Hae Nahm  ;  Hyungjin Rhee  ;  Haeryoung Kim  ;  Jeong Eun Yoo  ;  Jee San Lee  ;  Youngsic Jeon  ;  Gi Hong Choi  ;  Young Nyun Park 
 ONCOTARGET , Vol.8(59) : 99359-99371, 2017 
Journal Title
Issue Date
biopsy ; hepatocellular carcinoma ; stemness ; transarterial chemoembolization ; tumor stroma
Background: Hepatocellular carcinomas (HCCs) expressing stemness markers are characterized by an aggressive behavior, which might be promoted by an altered tumor stroma. Transarterial chemoembolization (TACE) induces severe hypoxia, and its effect on stemness and tumor stroma of HCCs remains unclear. The purpose of this study was to evaluate the sequential changes of stemness and tumor stroma under TACE-induced hypoxia using biopsy and resection-matched HCCs. Methods: Forty-six biopsy and resection matched HCCs including 10 cases with and 36 cases without preoperative TACE were selected. Immunohistochemistry for stemness (keratin 19 [K19], epithelial cell adhesion molecule [EpCAM], and CD133), hypoxia (carbonic anhydrase IX [CAIX] and vascular endothelial growth factor [VEGF]), and tumor stromal (α-smooth muscle actin [α-SMA] and fibroblast activation protein [FAP]) markers were performed and compared in matched biopsied and resected HCCs with and without TACE. Results: The accuracy of K19, EpCAM, CD133, CAIX, VEGF, α-SMA and FAP detected on biopsied HCCs was 64% ∼ 86%, using the expression status in resected HCCs as a reference standard in non-TACE group. The sequential change of hypoxia, stemness and stromal marker expression in matched biopsied and resected HCC was greater in TACE group than in non-TACE group (P < 0.05 for all). The degree of stemness marker expression was well correlated with those of tumor stromal markers, and the degree of CAIX expression was well correlated with that of K19 (P < 0.05). Conclusions: Stemness marker expression is considered to be increased along with tumor stromal alteration under TACE-induced hypoxia, which might promote the aggressive biology of HCC.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Nahm, Ji Hae(남지해) ORCID logo https://orcid.org/0000-0003-0902-866X
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Yoo, Jeong Eun(유정은)
Rhee, Hyungjin(이형진) ORCID logo https://orcid.org/0000-0001-7759-4458
Choi, Gi Hong(최기홍) ORCID logo https://orcid.org/0000-0002-1593-3773
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