Department of Biostatistics, H. Lee Moffitt Cancer Center, Tampa, FL, USA.
Urology. 2011 Oct;78(4):971.e1-9. doi: 10.1016/j.urology.2011.04.055. Epub 2011 Jul 29.
To understand the role in prostate cancer risk and aggressiveness, we investigated the expression in prostate tumor and single nucleotide polymorphisms of SLC5A8. Previous studies have suggested that SLC5A8 might function as a tumor suppressor gene, whose silencing by epigenetic changes might contribute to carcinogenesis.
We constructed tissue microarrays from 183 prostate tumor tissues, 43 adjacent non-neoplastic tissues from the same patients, and 13 tissue samples from patients with benign prostatic hyperplasia or prostatic intraepithelial neoplasia. A semiquantitative assessment of SLC5A8 protein expression was determined as the product of immunostaining intensity and the percentage of cells stained. In addition, we compared the frequencies of 4 single nucleotide polymorphisms (rs164365, rs1709189, rs1399236, and rs1681096) in SLC5A8 between 668 prostate cancer cases and 385 controls.
SLC5A8 expression was significantly greater in the tumor tissues than in the paired non-neoplastic tissues (P < .0001). In the Moffitt samples, we observed a borderline moderate risk increase in patients with a genotype containing ≥1 "A" allele of rs164365 (odds ratio 1.35, 95% confidence interval 1.00-1.80), especially among tall men (≥70 in.; odds ratio 1.80, 95% confidence interval 1.20-2.68). However, these results were not confirmed in the Cancer Genetic Markers of Susceptibility population.
These data suggest that the expression pattern of SLC5A8 might be used as a diagnostic biomarker, and a larger study is required to assess the importance of SLC5A8 single nucleotide polymorphisms in prostate cancer.
为了探究 SLC5A8 在前列腺癌风险和侵袭性中的作用，我们研究了 SLC5A8 在前列腺肿瘤组织中的表达和单核苷酸多态性。先前的研究表明，SLC5A8 可能作为一种肿瘤抑制基因发挥作用，其表观遗传沉默可能导致癌变。
我们构建了 183 例前列腺癌组织、43 例来自同一患者的癌旁非肿瘤组织和 13 例良性前列腺增生或前列腺上皮内瘤变患者组织的组织微阵列。通过免疫染色强度和染色细胞百分比的乘积来确定 SLC5A8 蛋白表达的半定量评估。此外，我们比较了 668 例前列腺癌病例和 385 例对照中 SLC5A8 的 4 个单核苷酸多态性（rs164365、rs1709189、rs1399236 和 rs1681096）的频率。
SLC5A8 在肿瘤组织中的表达明显高于配对的非肿瘤组织（P<0.0001）。在 Moffitt 样本中，我们观察到 rs164365 基因型中含有≥1 个“A”等位基因的患者发生中度风险增加（比值比 1.35，95%置信区间 1.00-1.80），尤其是在高个子男性中（≥70 英寸；比值比 1.80，95%置信区间 1.20-2.68）。然而，这些结果在癌症遗传易感性标记物人群中并未得到证实。
这些数据表明，SLC5A8 的表达模式可用作诊断生物标志物，需要进行更大规模的研究来评估 SLC5A8 单核苷酸多态性在前列腺癌中的重要性。
