Candidate serum biomarkers for prostate adenocarcinoma identified by mRNA differences in prostate tissue and verified with protein measurements in tissue and blood.
Candidate serum biomarkers for prostate adenocarcinoma identified by mRNA differences in prostate tissue and verified with protein measurements in tissue and blood.
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DOI：
10.1373/clinchem.2011.171637
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发表时间：
2012-03
影响因子：
9.3
通讯作者：
Klee GG
中科院分区：
文献类型：
--
作者：
Klee EW;Bondar OP;Goodmanson MK;Dyer RB;Erdogan S;Bergstralh EJ;Bergen HR 3rd;Sebo TJ;Klee GG
需要改进检测和治疗前列腺癌的方法。我们假设前列腺组织中的差异基因表达可以帮助识别前列腺癌的候选血液生物标志物，并且晚期前列腺疾病患者的血液可以用来验证它们在血液循环中的存在。候选标记物通过激光捕获显微解剖前列腺组织的mRNA表达模式进行鉴定。使用免疫组织化学（IHC）证实了具有商业抗血清的候选亚群的组织表达。组织提取物采用串联质谱法（MS/MS）进行分析。采用免疫测定法和胰蛋白酶消化、免疫提取肽的质谱联用法测定血药浓度。我们选择了35个新的候选前列腺腺癌生物标志物。13种IHC商用抗血清标记物的组织表达均得到证实，其中6种标记物在正常组织和恶性组织之间存在统计学差异。在组织提取物中，仅检测到其中的5种标记物。35种候选标记物中有16种在血液中成功检测。与对照组相比，ELISA测量的8种生物标志物中的4种和靶向MS测量的10种生物标志物中的3种显示晚期前列腺癌患者血药浓度显著升高。通过前列腺组织中基因表达谱鉴定出的七种新型生物标志物显示，与对照组相比，晚期前列腺癌患者血液中的APOC1、ASPN、COMP、CXCL11、CXCL9、F5和PCSK6的水平有统计学意义上的显著增加。
Improved tests are needed for detection and management of prostate cancer. We hypothesized that differential gene expression in prostate tissue could help identify candidate blood biomarkers for prostate cancer and that blood from men with advanced prostate disease could be used to verify their presence in circulation. Candidate markers were identified using mRNA expression patterns from laser-capture microdissected prostate tissue. Tissue expression was confirmed using immunohistochemistry (IHC) for the subset of candidates having commercial antisera. Tissue extracts were analyzed with tandem mass spectrometry (MS/MS). Blood concentrations were measured using immunoassays and MS/MS of trypsin-digested, immuno-extracted peptides. Thirty-five novel candidate prostate adenocarcinoma biomarkers were selected. Tissue expression was confirmed for all of the 13 markers having commercial antisera for IHC and six of these markers showed statistical discrimination between normal and malignant tissue. Only 5 of these markers were detected in tissue extracts using MS/MS. Sixteen of the 35 candidate markers were successfully assayed in blood. Four of eight biomarkers measured with ELISA and 3 of 10 biomarkers measured by targeted MS showed statistically significant increases in blood concentrations of advanced prostate cancer cases, compared to controls. Seven novel biomarkers identified by gene expression profiles in prostate tissue were shown to have statistically significant increased levels in blood from men with advanced prostate adenocarcinoma compared to controls: APOC1, ASPN, COMP, CXCL11, CXCL9, F5, and PCSK6.
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影响因子：
4.4
作者：
Anderson, NL;Anderson, NG;Pearson, TW
通讯作者：
Pearson, TW
影响因子：
6
作者：
Romanuik, Tammy L.;Ueda, Takeshi;Sadar, Marianne D.
通讯作者：
Sadar, Marianne D.
影响因子：
4.3
作者：
Julenius, K;Molgaard, A;Brunak, S
通讯作者：
Brunak, S
影响因子：
--
作者：
Kube DM;Savci-Heijink CD;Lamblin AF;Kosari F;Vasmatzis G;Cheville JC;Connelly DP;Klee GG
通讯作者：
Klee GG
综合基因组数据挖掘，发现潜在的血源性生物标志物，用于癌症的早期诊断。
影响因子：
3.7
作者：
Yang, Yongliang;Iyer, Lakshmanan K.;Adelstein, S. James;Kassis, Amin I.
通讯作者：
Kassis, Amin I.