The molecular connection of histopathological heterogeneity in hepatocellular carcinoma: A role of Wnt and Hedgehog signaling pathways

• DOI: 10.1371/journal.pone.0208194
• Publication Date: 2018-12-04T18:29:26Z
• Authors: Anindita Tripathy; Sudhir Thakurela; Manoj Kumar Sahu; Kanishka Uthanasingh; Manas Behera; Amrendra Kumar Ajay; Ratna Kumari
• Keywords: Tumor progression; Tumor promotion

Background Hepatocellular carcinoma (HCC) is leading cause of cancer-related mortality and categorized among the most common malignancies around world. It a heterogeneous tumor, which shows significant degree histopathological heterogeneity. Despite apparent diversity there has been very little distinct correlation between features molecular aberrations particularly when it comes to expression level Wnt Hh pathway molecules. The role pathways in relation HCC behavior viz. heterogeneity aggressiveness not known. Determining sequential changes associated characteristic during initiation, promotion, progression would probably lead better treatment prognosis. Methods N-Nitrosodiethylamine (DEN) induced model male Wistar rats were established study molecules different stages hepatocarcinogenesis. Their levels checked at mRNA protein HCC. correlated with biospecimens patients stages. Results In present we identified comprehensive change pattern DEN rodent hepatocarcinogenesis model. Our results demonstrate that β-catenin /CTNNB1 plays important tumor initiation promotion by stimulating cell proliferation. activated signaling early stage well-differentiated histological pattern. activity although but significantly increased both & moderately-differentiated was simultaneously linked an MMP9. Furthermore, our data demonstrated modestly down-regulated sustained turn aggressive invasive phenotype poorly-differentiated histopathology. Conclusion uncovers grade related potential utility these signatures daily clinical practice decide best therapy according characteristic. Additionally, offer insight into interaction triggers development progression.