Association of Specific Genotypes in Metastatic Suppressor HTPAP with Tumor Metastasis and Clinical Prognosis in Hepatocellular Carcinoma

作者：Ren Ning; Wu Jin Cai; Dong Qiong Zhu; Sun Hai Jing; Jia Hu Liang; Li Guo Cai; Sun Bing Sheng; Dai Chun; Shi Jiong; Wei Jin Wang; Sheng Yuan Yuan; Zhou Hai Jun; Ye Qing Hai; Qin Lun Xiu^*

来源：Cancer Research, 2011, 71(9): 3278-3286.

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 vertical bar 357 GG vertical bar 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. Cancer Res; 71(9); 3278-86.

• 出版日期2011-5-1
• 单位复旦大学