Abstract
Abstract Background and aim: Mounting evidence suggest that hepatocellular carcinoma (HCC) contains a subset of cells possessing some functional properties similar to normal tissue stem cells, usually referred as cancer stem cells (CSCs). THY1 (aka CD90) is involved in tumor-genesis and is commonly acknowledged as a maker of CSC in HCC. HMGA1, an HMG (high mobility group) chromatin-remodelling protein, has been recently highlighted as a key player in stem cell biology. HMGA1 overexpression induces malignant transformation in vitro and is deregulated in many cancer entities. This study aims to address the interrelated role of HMGA1 and THY1 in HCC. Methods: Using a global transcriptomic profiling (Affymetrix), validated by RT-qPCR, we analysed HMGA1 and THY1 expression levels in a cohort of HCC needle biopsy matched with corresponding non-neoplastic liver (total n=118) and normal liver (n=5). Using tissue microarray (TMA) technology, we evaluated by immunohistochemical staining HMGA1 and THY1 protein levels in a large collective of liver specimens (n=434, of which n=216 were HCCs). Results: We observed that both HMGA1 and THY1 expression is significantly up regulated in a subset of HCC specimens, correlating with metastatic disease and histological grading. Additionally, we demonstrate that high HMGA1 protein levels along with THY1 positivity in HCC samples results in unfavorable patients' outcome and disease progression. Conclusion: With this work we provide new evidence for HMGA1 and THY1 involvement in HCC progression and disease outcome and set the basis for further studies aiming to address their role in CSC biology of HCC. Citation Format: Mariacarla Andreozzi, Luca Quagliata, David Benz, Francesca Trapani, Serenella Eppenberger-Castori, Christian Ruiz, Pierlorenzo Pallante, Markus Heim, Luigi Tornillo, Alfredo Fusco, Salvatore Piscuoglio, Luigi Maria Terracciano. Enhanced expression of HMGA1 and THY1 in human hepatocellular carcinoma correlates with poor prognosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1386. doi:10.1158/1538-7445.AM2014-1386
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