Abstract
BackgroundHepatocellular 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.MethodsForty-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.ResultsThe 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).ConclusionsStemness marker expression is considered to be increased along with tumor stromal alteration under TACE-induced hypoxia, which might promote the aggressive biology of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the seventh most common malignancy worldwide, and the third greatest cause of cancer related mortality, especially in Asia and sub-Saharan Africa [1, 2]
The accuracy of keratin 19 (K19), epithelial cell adhesion molecule (EpCAM), cluster of differentiation 133 (CD133), carbonic anhydrase IX (CAIX), vascular endothelial growth factor (VEGF), α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) detected on biopsied HCCs was 64% ~ 86%, using the expression status in resected HCCs as a reference standard in non-Transarterial chemoembolization (TACE) group
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
Summary
Hepatocellular carcinoma (HCC) is the seventh most common malignancy worldwide, and the third greatest cause of cancer related mortality, especially in Asia and sub-Saharan Africa [1, 2]. Transarterial chemoembolization (TACE) is a popular loco-regional therapy in downstaging or bridging to make curative treatments (e.g. resection, transplantation) of HCC possible [3]. Increased expression of stemness-related markers was reported in resected/explanted HCCs after TACE treatment [16, 17]. 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.
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