Secretory phospholipase A2-IIa is a target gene of the HER/HER2-elicited pathway and a potential plasma biomarker for poor prognosis of prostate cancer.
Secretory phospholipase A2-IIa is a target gene of the HER/HER2-elicited pathway and a potential plasma biomarker for poor prognosis of prostate cancer.
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DOI：
10.1002/pros.22463
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发表时间：
2012-07-01
期刊：
影响因子：
2.8
通讯作者：
Lu, Shan
中科院分区：
文献类型：
--
作者：
Oleksowicz, Leslie;Liu, Yin;Bracken, R. Bruce;Gaitonde, Krishnanath;Burke, Barbara;Succop, Paul;Levin, Linda;Dong, Zhongyun;Lu, Shan
关键词：
我们前期的研究表明前列腺癌细胞过度表达和分泌分泌型磷脂酶A2 Ⅱ a（sPLA 2-IIa），前列腺癌患者血浆sPLA 2-IIa水平升高。本研究进一步探讨了sPLA 2-IIa过表达的潜在机制以及sPLA 2-IIa作为前列腺癌生物标志物的潜在作用。分析来自前列腺癌患者的血浆和组织样本的sPLA 2-IIa水平。Western blot和报告基因分析检测Heregulin-α对sPLA 2-IIa表达的调节作用。我们发现Heregulin-α通过HER 2/HER 3诱导的途径增强sPLA 2-IIa基因的表达。EGFR/HER 2双重抑制剂拉帕替尼和NF-kB抑制剂Bortezaline抑制Heregulin-α诱导的sPLA 2-IIa表达。Heregulin-α在转录水平上调sPLA 2-IIa基因的表达。我们进一步证实了由携带人前列腺癌异种移植物的小鼠分泌的血浆sPLA 2-IIa达到可检测的血浆浓度。受试者工作特征（ROC）分析显示，血浆sPLA 2-IIa水平高（最佳临界值为2.0ng/ml）的前列腺癌患者Gleason评分高（8~10），Gleason评分中等（6~7），而前列腺癌患者Gleason评分高（8~10），Gleason评分低（6~7），而前列腺癌患者Gleason评分高（8~10），Gleason评分低（6 ~ 7）。ROC曲线下面积（AUC）分别为0.73和0.74。我们发现，Heregulin-α，除了EGF，有助于sPLA 2-IIa在前列腺癌细胞中的过表达。我们的研究结果支持了这样的观点，即高水平的血浆sPLA 2-IIa可能作为一种预后不良的生物标志物，能够区分侵袭性前列腺癌和惰性前列腺癌，这可能会改善决策和优化患者管理。
Our previous study showed that prostate cancer cells overexpress and secrete secretory phospholipases A2 group IIa (sPLA2-IIa) and plasma sPLA2-IIa was elevated in prostate cancer patients. The current study further explored the underlying mechanism of sPLA2-IIa overexpression and the potential role of sPLA2-IIa as a prostate cancer biomarker. Plasma and tissue specimens from prostate cancer patients were analyzed for sPLA2-IIa levels. Regulation of sPLA2-IIa expression by Heregulin-α was determined by western blot and reporter assay. We found that Heregulin-α enhanced expression of the sPLA2-IIa gene via the HER2/HER3-elicited pathway. The EGFR/HER2 dual inhibitor Lapatinib and the NF-kB inhibitor Bortezomib inhibited sPLA2-IIa expression induced by Heregulin-α. Heregulin-α upregulated expression of the sPLA2-IIa gene at the transcriptional level. We further confirmed that plasma sPLA2-IIa secreted by mouse bearing human prostate cancer xenografts reached detectable plasma concentrations. A Receiver Operating Characteristic (ROC) analysis of patient plasma specimens revealed that high levels of plasma sPLA2-IIa, with the optimum cutoff value of 2.0 ng/ml, were significantly associated with high Gleason score (8~10) relative to intermediate Gleason score (6~7) prostate cancers and advanced relative to indolent cancers. The area under the ROC curve (AUC) was 0.73 and 0.74, respectively. We found that Heregulin-α, in addition to EGF, contributes to sPLA2-IIa overexpression in prostate cancer cells. Our findings support the notion that high levels of plasma sPLA2-IIa may serve as a poor prognostic biomarker capable of distinguishing aggressive from indolent prostate cancers, which may improve decision making and optimize patient management.
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影响因子：
254.7
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
82.9
作者：
Craft, N;Shostak, Y;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
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作者：
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胞质磷脂酶A2-Alpha：前列腺癌的潜在治疗靶标。
DOI：
10.1158/1078-0432.ccr-08-0566
发表时间：
2008-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Patel MI;Singh J;Niknami M;Kurek C;Yao M;Lu S;Maclean F;King NJ;Gelb MH;Scott KF;Russell PJ;Boulas J;Dong Q
通讯作者：
Dong Q