Exploring the involvement of FGFR4 in hepatocellular carcinoma

摘要: C73 Hepatocellular carcinoma (HCC) is a major malignancy inflicting most ethnicities with close to half million fatalities annually. While the etiology of disease relatively well-established (mostly due viral hepatitis and chronic liver injuries), progression treatment still poorly understood under-explored. Hence, we investigated contributory role FGFR4 HCC, member fibroblast growth factor receptor family that has been recently associated melanoma, breast head neck carcinoma. also presents unique interest HCC because tissue type highest mRNA expression FGFR4. We performed comprehensive resequencing entire coding region in 62 tumor-normal pairs, quantified their respective transcript by real-time PCR. found 4 novel genetic alterations (D126N, T179A, G426D, D709G) as well dominant representation two known polymorphisms among patients (V10I G338R). Increased was observed tumor tissues compared adjacent normal 31.6% patients. Correlation studies available clinical follow-ups revealed an increased α-fetoprotein (AFP) production bearing homozygous Arg388 allele, observation suggestive progression. vitro were subsequently confirm siRNA administration significantly reduced AFP HuH7, high AFP-producing cell line. Stimulation HepG2 cells (low AFP-producing) FGF19, specific ligand, AFP. These effects independent from impact activities on proliferation. In summary, our data (both vivo vitro) demonstrated may represent drug target against HCC. The signal transduction pathways implicated will require further investigation.