Metabolomic characterization of human prostate cancer bone metastases reveals increased levels of cholesterol.
Metabolomic characterization of human prostate cancer bone metastases reveals increased levels of cholesterol.
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DOI：
10.1371/journal.pone.0014175
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发表时间：
2010-12-03
期刊：
影响因子：
3.7
通讯作者：
Wikström P
中科院分区：
文献类型：
--
作者：
Thysell E;Surowiec I;Hörnberg E;Crnalic S;Widmark A;Johansson AI;Stattin P;Bergh A;Moritz T;Antti H;Wikström P
骨转移是前列腺癌（PCa）的一个重要临床特征。目前的诊断方法不能预测转移性前列腺癌在疾病的可治愈阶段。因此，鉴定参与骨转移生长的代谢途径有可能改善前列腺癌的预后和治疗。将代谢组学应用于前列腺癌骨转移（n = 20）与相应的正常骨（n = 14）进行比较，并进一步研究恶性（n = 13）和良性（n = 17）前列腺组织和相应的血浆样本，这些样本来自确诊转移的患者（n = 15）和未确诊转移的患者（n = 13）以及良性前列腺疾病患者（n = 30）。使用气相色谱-质谱法进行样品表征，使用化学计量学生物信息学进行数据分析。结果在一个单独的测试集中得到验证，该测试集包括来自其他癌症患者的转移性和正常骨组织（n = 7）。前列腺癌骨转移、其他癌症骨转移和正常骨之间存在显著差异。此外，我们在原发性肿瘤组织和血浆中发现了与转移性疾病显著相关的代谢物。在前列腺癌骨转移的代谢物中，尤其是胆固醇被注意到。在一组测试中，前列腺癌骨转移的平均胆固醇水平为127.30 mg/g，而不同来源的骨转移和正常骨的平均胆固醇水平分别为81.06和35.85 mg/g （P = 0.0002和0.001）。前列腺癌骨转移灶的免疫组织化学染色显示肿瘤上皮细胞中低密度脂蛋白受体和B类1型清除率受体和3-羟基-3-甲基戊二酰辅酶还原酶水平变化，表明胆固醇可能内流和重新合成。我们已经确定了与前列腺癌转移相关的代谢物，特别是在前列腺癌骨转移中发现了高水平的胆固醇。根据我们的发现和先前的文献，这使得胆固醇可能成为晚期前列腺癌的治疗靶点。
Metastasis to the bone is one clinically important features of prostate cancer (PCa). Current diagnostic methods cannot predict metastatic PCa at a curable stage of the disease. Identification of metabolic pathways involved in the growth of bone metastases therefore has the potential to improve PCa prognostication as well as therapy. Metabolomics was applied for the study of PCa bone metastases (n = 20) in comparison with corresponding normal bone (n = 14), and furthermore of malignant (n = 13) and benign (n = 17) prostate tissue and corresponding plasma samples obtained from patients with (n = 15) and without (n = 13) diagnosed metastases and from men with benign prostate disease (n = 30). This was done using gas chromatography-mass spectrometry for sample characterization, and chemometric bioinformatics for data analysis. Results were verified in a separate test set including metastatic and normal bone tissue from patients with other cancers (n = 7). Significant differences were found between PCa bone metastases, bone metastases of other cancers, and normal bone. Furthermore, we identified metabolites in primary tumor tissue and in plasma which were significantly associated with metastatic disease. Among the metabolites in PCa bone metastases especially cholesterol was noted. In a test set the mean cholesterol level in PCa bone metastases was 127.30 mg/g as compared to 81.06 and 35.85 mg/g in bone metastases of different origin and normal bone, respectively (P = 0.0002 and 0.001). Immunohistochemical staining of PCa bone metastases showed intense staining of the low density lipoprotein receptor and variable levels of the scavenger receptor class B type 1 and 3-hydroxy-3-methylglutaryl-coenzyme reductase in tumor epithelial cells, indicating possibilities for influx and de novo synthesis of cholesterol. We have identified metabolites associated with PCa metastasis and specifically identified high levels of cholesterol in PCa bone metastases. Based on our findings and the previous literature, this makes cholesterol a possible therapeutic target for advanced PCa.
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影响因子：
37.3
作者：
Denkert C;Budczies J;Weichert W;Wohlgemuth G;Scholz M;Kind T;Niesporek S;Noske A;Buckendahl A;Dietel M;Fiehn O
通讯作者：
Fiehn O
影响因子：
6.6
作者：
Issaq, Haleem J.;Nativ, Ofer;Mullerad, Michael
通讯作者：
Mullerad, Michael
影响因子：
7.4
作者：
Jiye, A;Trygg, J;Moritz, T
通讯作者：
Moritz, T
影响因子：
4.4
作者：
Jonsson, Par;Johansson, Elin Sjovik;Antti, Henrik
通讯作者：
Antti, Henrik
影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL