Association of Specific Genotypes in Metastatic Suppressor HTPAP with Tumor Metastasis and Clinical Prognosis in Hepatocellular Carcinoma
Association of Specific Genotypes in Metastatic Suppressor HTPAP with Tumor Metastasis and Clinical Prognosis in Hepatocellular Carcinoma
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转移抑制因子 HTPAP 中特定基因型与肝细胞癌肿瘤转移和临床预后的关联。
DOI：
10.1158/0008-5472.can-10-3100
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发表时间：
2011-05-01
期刊：
影响因子：
11.2
通讯作者：
Qin, Lun-Xiu
中科院分区：
文献类型：
--
作者：
Ren, Ning;Wu, Jin-Cai;Qin, Lun-Xiu
磷脂酸磷酸酶HTPAP已被定义为肝细胞癌（HCC）的转移抑制因子，但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例接受HCC切除术的患者的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。针对两个tagSNPs（+357 G/C和+1838 A/G），我们发现只有+357 G/C基因型与HTPAP mRNA和蛋白表达水平以及转移概率显著相关。在665例HCC患者的独立队列中，我们确定+357G/C基因型与较短的复发时间和总生存期相关。总之，这些结果表明HTPAP tagSNP +357 GG+GC基因型可能通过下调HTPAP表达来影响HCC转移潜能和临床预后。扩展这些结果，全局表达谱分析鉴定了41个基因，包括在+357 GG+GC组中显著过表达的促炎基因IL-8和TLR 2，作为可能与HTPAP共调节的标记物。总之，我们的研究结果确定了HTPAP基因型和相关基因表达模式，有利于转移进展，并可用于预测肝癌患者的肿瘤转移和预后。
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.