Zhongshan Hospital, Fudan University, Shanghai, China.
Cancer Res. 2011 May 1;71(9):3278-86. doi: 10.1158/0008-5472.CAN-10-3100.
The phosphatidic acid phosphatase HTPAP has been defined as a metastatic suppressor of hepatocellular carcinoma (HCC), but little is known about its function or potential applications as a prognostic marker. In this study, we analyzed patterns of HTPAP genetic variation and gene expression in 864 patients who underwent HCC resection, assessing these patterns for correlations to tumor metastasis potential. Focusing on two tagSNPs that were selected (+357G/C and +1838A/G), we found that only the +357G/C genotype was significantly associated with HTPAP mRNA and protein expression levels and the probability of metastasis. In an independent cohort of 665 HCC patients, we determined that the +357G/C genotype was associated with shorter time to recurrence and overall survival. Together, these results indicated that the HTPAP tagSNP +357 GG+GC genotypes may influence HCC metastatic potential and clinical prognosis by down-regulating HTPAP expression. Extending these results, a global expression profiling analysis identified 41 genes including the pro-inflammatory genes IL-8 and TLR2 that were significantly overexpressed in the +357 GG+GC group, as possible coregulated markers with HTPAP. Together, our findings identify an HTPAP genotype and associated gene expression pattern that favors metastasis progression and that could be used to predict tumor metastasis and prognosis in HCC patients.
磷酸酶 HTAP 在肝癌（HCC）中被定义为一种转移性抑制物，但对于其功能或作为预后标志物的潜在应用知之甚少。在这项研究中，我们分析了 864 名接受 HCC 切除术患者的 HTPAP 遗传变异和基因表达模式，评估这些模式与肿瘤转移潜力的相关性。我们专注于两个被选择的标签 SNP（+357G/C 和 +1838A/G），发现只有 +357G/C 基因型与 HTPAP mRNA 和蛋白表达水平以及转移的可能性显著相关。在一个由 665 名 HCC 患者组成的独立队列中，我们确定了+357G/C 基因型与复发时间和总生存期较短有关。总的来说，这些结果表明，HTPAP 标签 SNP +357 GG+GC 基因型可能通过下调 HTPAP 表达来影响 HCC 的转移潜力和临床预后。扩展这些结果，一个全局表达谱分析确定了 41 个基因，包括促炎基因 IL-8 和 TLR2，在 +357 GG+GC 组中显著过表达，可能是与 HTPAP 共同调控的标记物。总之，我们的研究结果确定了一种有利于转移进展的 HTPAP 基因型和相关基因表达模式，可用于预测 HCC 患者的肿瘤转移和预后。
