可能预测非裔美国前列腺癌男性侵袭性疾病的新型生物标志物特征。
Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer.
作者信息
Yamoah Kosj, Johnson Michael H, Choeurng Voleak, Faisal Farzana A, Yousefi Kasra, Haddad Zaid, Ross Ashley E, Alshalafa Mohammed, Den Robert, Lal Priti, Feldman Michael, Dicker Adam P, Klein Eric A, Davicioni Elai, Rebbeck Timothy R, Schaeffer Edward M
机构信息
Kosj Yamoah, Robert Den, and Adam P. Dicker, Thomas Jefferson University Hospital; Priti Lal, Michael Feldman, and Timothy R. Rebbeck, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Kosj Yamoah, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Michael H. Johnson, Farzana A. Faisal, Ashley E. Ross, and Edward M. Schaeffer, Johns Hopkins University, Baltimore, MD; Voleak Choeurng, Kasra Yousefi, Zaid Haddad, Mohammed Alshalafa, and Elai Davicioni, GenomeDx Biosciences, Vancouver, British Columbia, Canada; and Eric A. Klein, The Cleveland Clinic Foundation, Cleveland, OH.
出版信息
J Clin Oncol. 2015 Sep 1;33(25):2789-96. doi: 10.1200/JCO.2014.59.8912. Epub 2015 Jul 20.
PURPOSE
We studied the ethnicity-specific expression of prostate cancer (PC) -associated biomarkers to evaluate whether genetic/biologic factors affect ethnic disparities in PC pathogenesis and disease progression.
PATIENTS AND METHODS
A total of 154 African American (AA) and 243 European American (EA) patients from four medical centers were matched according to the Cancer of the Prostate Risk Assessment postsurgical score within each institution. The distribution of mRNA expression levels of 20 validated biomarkers reported to be associated with PC initiation and progression was compared with ethnicity using false discovery rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models. A conditional logistic regression model was used to evaluate the interaction between ethnicity and biomarkers for predicting clinicopathologic outcomes.
RESULTS
Of the 20 biomarkers examined, six showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04). Dysregulation of AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) as well as loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P = .037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner. Dysregulation of GOLM1 (P = .037), SRD5A2 (P = .023), and MKi67 (P = .023) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years. A greater proportion of AA men than EA men had triple-negative (ERG-negative/ETS-negative/SPINK1-negative) disease (51% v 35%; P = .002).
CONCLUSION
We have identified a subset of PC biomarkers that predict the risk of clinicopathologic outcomes in an ethnicity-dependent manner. These biomarkers may explain in part the biologic contribution to ethnic disparity in PC outcomes between EA and AA men.
目的
我们研究了前列腺癌（PC）相关生物标志物的种族特异性表达，以评估遗传/生物学因素是否影响PC发病机制和疾病进展中的种族差异。
患者与方法
来自四个医疗中心的154名非裔美国（AA）患者和243名欧美（EA）患者，在各机构内根据前列腺癌风险评估术后评分进行匹配。使用错误发现率、调整后的Wilcoxon-Mann-Whitney检验和逻辑回归模型，比较了20种已验证的与PC起始和进展相关的生物标志物的mRNA表达水平在不同种族间的分布情况。采用条件逻辑回归模型评估种族与生物标志物之间的相互作用对预测临床病理结果的影响。
结果
在检测的20种生物标志物中，有6种在一种或多种统计模型中显示出非裔美国男性与欧美男性之间具有统计学意义的差异表达。这些包括ERG（P <.001）、AMACR（P <.001）、SPINK1（P =.001）、NKX3-1（P =.03）、GOLM1（P =.03）和雄激素受体（P =.04）。AMACR（P =.036）、ERG（P =.036）、FOXP1（P =.041）和GSTP1（P =.049）的失调，以及肿瘤抑制因子NKX3-1（P =.025）和RB1（P =.037）的功能丧失突变，以种族依赖的方式预测了病理T3疾病的风险。GOLM1（P =.037）、SRD5A2（P =.023）和MKi67（P =.023）的失调预测了临床结果，包括3年生化复发和5年转移。非裔美国男性中三阴性（ERG阴性/ETS阴性/SPINK1阴性）疾病的比例高于欧美男性（51%对35%；P =.002）。
结论
我们确定了一组PC生物标志物，它们以种族依赖的方式预测临床病理结果的风险。这些生物标志物可能部分解释了欧美男性和非裔美国男性在PC结果的种族差异中的生物学贡献。
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