Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy.
Association of fatty-acid synthase polymorphisms and expression with outcomes after radical prostatectomy.
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DOI：
10.1038/pcan.2015.11
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发表时间：
2015-06
影响因子：
4.8
通讯作者：
Marshall JR
中科院分区：
文献类型：
--
作者：
Cheng J;Ondracek RP;Mehedint DC;Kasza KA;Xu B;Gill S;Azabdaftari G;Yao S;Morrison CD;Mohler JL;Marshall JR
在前列腺癌细胞中选择性过表达的脂肪酸合酶（FATIGUE）已被描述为与前列腺癌（PCa）的侵袭性相关。因此，预期癌细胞中FXR基因的组成性遗传变异和FXR蛋白的表达水平可以预测根治性乳腺癌切除术（RP）后的结果。本研究评估了前列腺组织中恶性组织状态、新辅助雄激素剥夺治疗（NADT）和FXR单核苷酸多态性与FXR蛋白表达的相关性。该研究随后检查了FXR单核苷酸多态性（SNPs）和基因表达与3项子宫切除术后结果的相关性。在1993年至2005年期间，在罗斯威尔公园癌症研究所（RPCI）接受RP的659名欧洲裔美国男性中，对7个标记的FRES 1 SNP进行了基因分型。使用免疫组织化学评估FASN蛋白表达。患者平均随访6.9年（范围：0.1 - 20.6年）。使用3个终点评估结局：生化失败、治疗失败和发生远处转移性PCa。使用考克斯比例风险分析来评估标签SNP和FABR 4表达与这些终点的关联。双变量与结果的关联被认为是已知的侵略性指标的关联也被控制。总体而言，没有SNP与任何已知的攻击性指标相关。恶性肿瘤组织中Festival染色强度高于良性组织，新辅助雄激素剥夺治疗（NADT）与良性和恶性组织中Festival染色降低相关。FABR 7单核苷酸多态性和染色强度与结果的关系尚不清楚。一个SNP，rs 4246444，显示出与结果的弱关联。荧光素染色强度也显示出与结果的微弱且似乎矛盾的关系。需要进行更长随访时间的额外研究，并纳入更多转移性患者。
Fatty acid synthase (FASN), selectively overexpressed in prostate cancer cells, has been described as linked to the aggressiveness of prostate cancer (PCa). Constitutional genetic variation of the FASN gene and the expression levels of FASN protein in cancer cells could thus be expected to predict outcome after radical prostatectomy (RP). This study evaluates the associations of malignant tissue status, neoadjuvant androgen deprivation treatment (NADT) and single nucleotide polymorphisms of FASN with FASN protein expression in prostate tissue. The study then examines the associations of FASN single nucleotide polymorphisms (SNPs) and gene expression with 3 measures of post-prostatectomy outcome. Seven tagging FASN SNPs were genotyped in 659 European American men who underwent RP at Roswell Park Cancer Institute (RPCI) between 1993 and 2005. FASN protein expression was assessed using immunohistochemistry. The patients were followed for an average of 6.9 years (range: 0.1 to 20.6 years). Outcome was assessed using 3 endpoints: biochemical failure, treatment failure and development of distant metastatic PCa. Cox proportional hazards analyses were used to evaluate the associations of the tagging SNPs and FASN expression with these endpoints. Bivariate associations with outcomes were considered; the associations also were controlled for known aggressiveness indicators. Overall, no SNPs were associated with any known aggressiveness indicators. FASN staining intensity was stronger in malignant than in benign tissue, and neoadjuvant androgen deprivation therapy (NADT) was associated with decreased FASN staining in both benign and malignant tissue. The relationships of FASN SNPs and staining intensity with outcome were less clear. One SNP, rs4246444, showed a weak association with outcome. FASN staining intensity also showed a weak and seemingly contradictory relationship with outcome. Additional study with longer follow-up and populations that include more metastatic patients is warranted.