Downregulation of HTPAP transcript variant 1 correlates with tumor metastasis and poor survival in patients with hepatocellular carcinoma
Downregulation of HTPAP transcript variant 1 correlates with tumor metastasis and poor survival in patients with hepatocellular carcinoma
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DOI：
10.1111/j.1349-7006.2011.01863.x
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发表时间：
2011-03-01
期刊：
影响因子：
5.7
通讯作者：
Qin, Lun-Xiu
中科院分区：
文献类型：
--
作者：
Dai, Chun;Dong, Qiong-Zhu;Qin, Lun-Xiu
我们之前的研究已确定 HTPAP 是一种来自 8p 染色体的新型转移抑制因子，该染色体在转移性 HCC 中经常被删除。我们试图通过使用特异性 TaqMan 探针和引物组的 RT-PCR 进一步评估 HTPAP 转录变异体（HTPAP-1、HTPAP-2 和 HTPAP-3）在 67 个 HCC 肿瘤组织和 11 个正常肝组织中的表达水平，并探讨它们与 HCC 转移和生存的关系。我们发现 HCC 中三种 HTPAP 转录变异体的表达水平差异很大。仅 HTPAP-1 被发现与 HCC 转移 (P = 0.00053)、总生存率 (P = 0.0023) 和复发时间 (P = 0.010) 显着相关。 HTPAP-1表达较低的患者易伴有肝内转移和癌栓（P < 0.05），预后较差。在体外，将编码HTPAP-1、HTPAP-2和HTPAP-3的三个融合pEGFP-N1载体分别引入HCC细胞中以追踪HTPAP的表达并鉴定其功能。我们发现HTPAP-1的过度表达使HCC细胞的侵袭能力降低，但对细胞增殖没有显着影响，并且在细胞膜和细胞质中也显示出独特的细胞位置，这与其他两种变体不同。因此，HTPAP-1可能是HTPAP的转录本，对HCC转移表现出抑制作用，并且可以作为HCC的预后标志物。 （《癌症科学》2011 年；102：583-590）
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. (Cancer Sci 2011; 102: 583-590)