Differential Expression of TWSG1, BMP4 and Shh Morphogens Signaling Proteins in Hepatocellular Carcinoma and Cholangiocellular Carcinoma
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Abstract
Hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCA) constitute two of the most common liver malignancies in adults. The molecular mechanisms underlying their development remain poorly understood. Morphogen proteins, including the hedgehog and the bone morphogenetic proteins pathway fulfill a major role in embryonic development. Consequently, alterations in these proteins may cause embryonic defects. Furthermore, abnormal expression of morphogen proteins is found to correlate with cancer development and progression. This thesis has demonstrated the differential expression and co-localization of the morphogen proteins, including sonic hedgehog (Shh), bone morphogenetic protein (BMP)-4 and twisted gastrulation protein (TWSG)-1 in human HCC and CCA tumors and cell lines. These proteins are strongly expressed in CCA more than in HCC. Overall, these findings suggest that morphogen proteins may play a crucial role during liver carcinogenesis and progression, specifically in CCA. Moreover, these proteins can serve as diagnostic biomarkers for HCC and CCA.