Key result
hnRNP A2/B1 overexpression is linked to hepatitis and HCC, with cytoplasmic localization correlating with dedifferentiation.
Why the study?
It is important to find a new biomarker that diagnoses hepatocellular carcinoma and monitors its treatment, with the antigen recognized by scFv N14 antibody previously unknown.
Observational (n=70)
Answers are grounded in this paper and cite their sources.
The increased expression and cytoplasmic localization of hnRNP A2/B1 may serve as a diagnostic biomarker for assessing the risk of human liver cancer.
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the world's leading causes of death among cancer patients. It is important to find a new biomarker that diagnoses HCC and monitors its treatment. In our previous work, we screened a single-chain antibody (scFv) N14, which could specifically recognize human HepG2 HCC cells but not human non-cancerous liver LO2 cells. However, the antigen it recognized in the cells remained unknown. METHODS: Recombinant scFv N14 antibody was expressed as an active antibody. Using this antibody with a combination of immunological and proteomic approaches, we identified the antigen of scFv N14 antibody as the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1). The expression of hnRNP A2/B1 in HCC cells was then investigated by semi-quantitative RT-PCR and immunohistochemistry. RESULTS: We found that the up-regulation of hnRNP A2/B1 was measured at both transcriptional and translational levels in rat HCC cells but not in rat hepatic cells. We also found that in various human hepatic tissues, hnRNP A2/B1 was highly expressed in both human hepatitis virus positive liver tissues and human HCC tissues but not in normal liver tissues. Interestingly, we observed that the localization of hnRNP A2/B1 in HCC cells was altered during the development of HCC. In human hepatitis virus infected tissues hnRNP A2/B1 resides exclusively in the nuclei of hepatocytes. However, when the HCC progressed from a well differentiated to a poorly differentiated stage, hnRNP A2/B1 was increasingly localized in the cytoplasm. In contrast, the HCC tissues with hnRNP A2/B1 highly expressed in the nucleus decreased. CONCLUSIONS: This work is the first to show that hnRNP A2/B1 is the antigen specifically recognized by the scFv N14 antibody in HCC cells. The over-expression of hnRNP A2/B1 was confirmed in cultured human and rat HCC cell lines, human virus related hepatitis liver tissues and human HCC tissues. The increased localization of hnRNP A2/B1 in the cytoplasm of HCC cells was revealed during the dedifferentiation of hepatocellular carcinoma. Therefore, we suggest that the increased expression and cytoplasmic localization of hnRNP A2/B1 can be used as a diagnostic biomarker to assess the risk of human liver cancer.
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Cui et al. (2010) conducted an observational in Hepatocellular carcinoma (n=70). Hepatocellular carcinoma and hepatitis vs. Normal liver tissues was evaluated on hnRNP A2/B1 expression positivity (p=<0.01). hnRNP A2/B1 was significantly overexpressed in human hepatitis and hepatocellular carcinoma tissues compared to normal liver (p<0.01), with increased cytoplasmic localization correlating with tumor dedifferentiation.
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