Gene expression analysis for evaluation of potential biomarkers in hepatocellular carcinoma

Abstract

Background: The poor prognosis of hepatocellular carcinoma (HCC) and the lack of specific screening markers underline the need for new biomarkers for human hepatocarcinogenesis.

Materials and methods: We investigated 10 postulated biomarkers for HCC (AFP, GPC3, OPN, IGF1, HGF, SPINK1, KPNA, FUCA1, CgA, HSP90) with microarray gene expression analysis and real-time polymerase chain reaction (RT-PCR) in HCC tissues of different etiologies.

Results: Four candidate genes (FUCA1, HGF, IGF1, CgA) showed low median fold changes (fc) of expression compared to corresponding non-malignant liver tissues (fc range=0.2-0.8; maximum 15% of samples). The classic biomarker, alpha-fetoprotein (AFP), was significantly over-expressed (fc=2.4) in 30% of tumors. High tumor AFP expression was associated with significantly elevated serum AFP concentrations (>90% of cases). Five genes (OPN, SPINK1, GPC3, HSP90, KNPA2) showed significantly higher expression than AFP in 64% to 82% of samples (median fc range=2.9-8.3). RT-PCR analyses gave similar results.

Conclusion: Unlike previous studies, our results did not confirm FUCA1, HGF, IGF1 or CgA as potential markers for HCC. In contrast, OPN, SPINK1, GPC3 and KNPA2 were significantly over-expressed in HCC tissues. These genes may be useful in developing future biomarkers and therapeutic strategies for HCC.

Keywords: Hepatocellular carcinoma; alpha-fetoprotein; biomarkers; gene expression analysis; glypican 3; osteopontin.