Downregulation of HTPAP transcript variant 1 correlates with tumor metastasis and poor survival in patients with hepatocellular carcinoma.

Our previous study has identified HTPAP as a novel metastasis suppressor from chromosome 8p which is often deleted in metastatic HCC. We sought to further evaluate the expression levels of transcript variants of HTPAP (HTPAP-1, HTPAP-2 and HTPAP-3) in 67 HCC tumor tissues and 11 normal liver tissues by RT-PCR with specific TaqMan probes and primer sets, and explore their association with HCC metastasis and survival. We found that the expression levels of three HTPAP transcript variants were quite different in HCCs. Only HTPAP-1 was found to be significantly associated with HCC metastasis (P=0.00053), overall survival (P=0.0023) and time to recurrence (P=0.010) of HCC. Patients with a lower expression of HTPAP-1 were inclined to accompany intrahepatic metastases and tumor thrombi (P<0.05) and had a poor prognosis. In vitro, three fusion pEGFP-N1 vectors encoding HTPAP-1, HTPAP-2 and HTPAP-3 were introduced into HCC cells respectively to track HTPAPs' expressions and identify their function. We found overexpression of HTPAP-1 conferred HCC cells reduced ability of invasion without significant impact on cell proliferation, and also displayed a distinct cell location on cell membrane and in cytoplasm, which were different from two other variants. Consequently, HTPAP-1 may be the transcript of HTPAP to exhibit a suppressive role on HCC metastasis, and can be a prognostic marker for HCC.