School of Life Sciences, Hormone-Dependent Cancer Research Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia.
Int J Gynecol Cancer. 2010 May;20(4):529-36. doi: 10.1111/IGC.0b013e3181d9273e.
Kallikrein-related peptidase 10 (KLK10) overexpression is a predictor of poor disease outcome in women with late-stage ovarian cancer. We aimed to identify whether KLK10 overexpression could be attributed to genetic variants, in particular, in hormone response elements or transcription factor binding sites.
Cox regression analysis was used to assess the association between 2 tag and 1 exonic KLK10 single nucleotide polymorphisms (SNPs) and the survival of 319 patients with ovarian cancer. Four different ovarian cancer cell lines were investigated for KLK10 expression after hormone stimulation, and sequence variation in the 3.6-Kb upstream of the KLK10 start site. In silico analyses of SNPs in cell lines and from published databases were undertaken to identify further research novel and potentially functional SNPs that are not covered by tag SNPs.
The KLK10 SNPs investigated were not associated with ovarian cancer survival. However, steroid hormone treatment of ovarian cell lines showed KLK10 up-regulation in response to estrogen and estrogen plus progesterone treatments in the aggressive cell line PEO1 and affirmed a role for KLK10 in aggressive ovarian cancer. Potentially functional KLK10 SNPs were identified by cell line sequencing and bioinformatic analysis.
Potentially functional candidate KLK10 SNPs require investigation in future association studies of ovarian cancer risk and survival, including rs3760738 identified in aggressive ovarian cancer cell lines and predicted to affect transcription factor binding sites.
激肽释放酶相关肽酶 10（KLK10）过表达是晚期卵巢癌女性疾病预后不良的预测因子。我们旨在确定 KLK10 过表达是否归因于遗传变异，特别是激素反应元件或转录因子结合位点的变异。
使用 Cox 回归分析评估了 2 个标签和 1 个外显子 KLK10 单核苷酸多态性（SNP）与 319 例卵巢癌患者生存之间的关联。研究了 4 种不同的卵巢癌细胞系在激素刺激后 KLK10 的表达情况，以及 KLK10 起始位点上游 3.6-Kb 的序列变异。对细胞系中的 SNP 进行了计算机分析，并从已发表的数据库中进行了分析，以确定进一步研究的新型潜在功能 SNP，这些 SNP 未被标签 SNP 涵盖。
所研究的 KLK10 SNP 与卵巢癌的生存无关。然而，甾体激素处理卵巢细胞系显示，在侵袭性细胞系 PEO1 中，雌激素和雌激素加孕激素处理可上调 KLK10，并证实 KLK10 在侵袭性卵巢癌中的作用。通过细胞系测序和生物信息学分析鉴定了潜在功能的 KLK10 SNP。
需要在未来的卵巢癌风险和生存的关联研究中进一步研究潜在功能的候选 KLK10 SNP，包括在侵袭性卵巢癌细胞系中鉴定的 rs3760738，该 SNP 预测会影响转录因子结合位点。
