title: Association of specific genotypes in metastatic suppressor HTPAP with tumor metastasis and clinical prognosis in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ren
authors.forename: Jin-Cai
authors.initials: JC
authors.lastname: Wu
authors.forename: Qiong-Zhu
authors.initials: QZ
authors.lastname: Dong
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Sun
authors.forename: Hu-Liang
authors.initials: HL
authors.lastname: Jia
authors.forename: Guo-Cai
authors.initials: GC
authors.lastname: Li
authors.forename: Bing-Sheng
authors.initials: BS
authors.lastname: Sun
authors.forename: Chun
authors.initials: C
authors.lastname: Dai
authors.forename: Jiong
authors.initials: J
authors.lastname: Shi
authors.forename: Jin-Wang
authors.initials: JW
authors.lastname: Wei
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Sheng
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Zhou
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Ye
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis; D010711:Phosphatidate Phosphatase / Q000096:biosynthesis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C406242:phosphatidic acid phosphatase type 2; D010711:Phosphatidate Phosphatase