The heterogeneous nature of hepatocellular carcinoma (HCC) and the lack of appropriate biomarkers have hampered patient prognosis and treatment stratification. To identify a new prognostic biomarker that is related to human telomerase reverse transcriptase (hTERT) in HCC, we employed a unique proteomics approach using liquid chromatograph‐mass spectrometry/mass spectrometry (LC‐MS/MS) after gel filtration purification of liver tissue.

Protein lysates from HCC and cirrhotic liver tissue were subjected to gel filtration using high performance liquid chromatography. The telomerase complex was identified at a molecular mass of 350 kDa in parallel with telomerase activity. These fractionated lysates of 350 kDa were analyzed by LC‐MS/MS. The relation of the identified marker and prognosis was statistically examined in surgically resected HCC patients.

We identified 24 differentially expressed proteins in HCC. One of these proteins, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1), was further analyzed by immunoprecipitation assay using tissue and cell line samples and found to interact with hTERT. Moreover small interfering RNA against hnRNP A2/B1 suppressed telomerase activity, and immunohistochemical examination showed that the enhanced nuclear and cytoplasmic hnRNP A2/B1 expression in HCC was significantly associated with histological grade of tumor differentiation and microvascular invasion of HCC. Furthermore, survival analysis of 74 HCC patients who received curative surgical treatment showed that hnRNP A2/B1 expression is an independent prognostic factor for patient survival.

Heterogeneous nuclear ribonucleoprotein A2/B1, an hTERT‐associated protein, is a potential prognostic biomarker for HCC patients and might be a therapeutic target of HCC.