Changes in Biomarkers of Inflammation and Angiogenesis During Androgen Deprivation Therapy for Prostate Cancer

• Published in: The oncologist (Dayton, Ohio) Vol. 17; no. 2; pp. 212 - 219
• Main Authors: Saylor, Philip J., Kozak, Kevin R., Smith, Matthew R., Ancukiewicz, Marek A., Efstathiou, Jason A., Zietman, Anthony L., Jain, Rakesh K., Duda, Dan G.
• Format: Journal Article
• Language: English
• Published: Durham, NC, USA AlphaMed Press 01.02.2012
• Subjects: Aged; Androgen Antagonists - therapeutic use; Biomarkers; Chemokine CXCL12 - blood; Fibroblast Growth Factor 2 - blood; Genitourinary Cancer: Prostate; Humans; Inflammation - blood; Inflammation - drug therapy; Interleukin-1beta - blood; Interleukin-6 - blood; Interleukin-8 - blood; Male; Neovascularization, Physiologic; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - physiopathology; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor Receptor-1 - blood
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2011-0321

Introduction. Angiogenesis and inflammation are both important to the pathogenesis of malignancies. Androgen deprivation therapy (ADT) for prostate cancer causes drastic hormonal changes that alter both disease and host factors. We measured inflammatory and angiogenic biomarkers in ADT‐treated and control groups of men with prostate cancer. Materials and Methods. Baseline and 12‐week plasma samples were collected from 37 ADT‐naïve men with locally advanced or recurrent prostate cancer. Of those, 23 initiated ADT with a gonadotropin‐releasing hormone (GnRH) agonist and 14 served as nontreatment controls. Samples were tested for a panel of angiogenic and inflammatory biomarkers. Results. The treatment group had significantly higher concentrations of the inflammatory biomarkers interleukin (IL)‐1β, IL‐6, IL‐8, tumor necrosis factor (TNF)‐α, and stromal cell–derived factor (SDF)‐1α. None of the angiogenic biomarkers were significantly different between the groups at baseline. Among patients with a short prostate‐specific antigen (PSA) doubling time (<6 months), the proangiogenic factor basic fibroblast growth factor (bFGF) was lower at baseline. In the treatment group, plasma placental growth factor (PlGF) increased and IL‐6 decreased after 12 weeks of ADT. Moreover, the treatment group continued to have significantly higher concentrations of the inflammatory biomarkers IL‐1β, IL‐8, and SDF‐1α as well as bFGF than controls. Discussion. These men were characterized by elevations in several traditional markers of aggressive disease and also by higher levels of several inflammatory biomarkers. Although ADT decreased IL‐6 levels, IL‐1β, IL‐8, and SDF‐1α remained significantly higher than in controls. The role of these biomarkers should be further explored. 摘要 前言. 血管生成和炎症对于恶性肿瘤的发病机制研究都是十分重要的。前列腺癌的雄激素剥夺疗法（ADT）会引起荷尔蒙的极端变化，从而使疾病和宿主因素都发生改变。我们测定了ADT治疗组和对照组的男性前列腺癌患者的炎症和血管生成生物标志物。 材料与方法. 收集37例既往未接受过ADT治疗的局部晚期或复发性前列腺癌男性患者的基线和12周血浆样本。其中，23例采用促性腺激素释放激素（GnRH）激动剂进行ADT治疗，14例作为非治疗对照。样品采用血管生成和炎症生物标志物进行一组检测。 结果. 治疗组的炎症生物标志物白细胞介素（IL）‐1β，IL‐6，IL‐8，肿瘤坏死因子（TNF）‐α，基质细胞衍生因子（SDF）‐1α的浓度显著升高。各组间血管生成生物标志物的基线水平无显著差异。在出现短暂前列腺特异抗原（PSA）倍增时间（<6个月）的患者中，作为促血管生成因子的碱性成纤维细胞生长因子（bFGF）基线水平较低。接受12周ADT后，治疗组的血浆胎盘生长因子（PlGF）水平提高，IL‐6水平下降。此外，与对照组相比，治疗组继续保持显著高浓度的炎症生物标志物IL‐1β，IL‐8和SDF‐1α，以及bFGF。 讨论. 这些患者均存在一些严重疾病的传统标志物以及几种炎症标志物水平升高的情况。虽然ADT降低了IL‐6水平，但IL‐1β，IL‐8和SDF‐1α水平仍明显高于对照组。对这些生物标志物的作用应进行进一步的深入探讨。 Inflammatory and angiogenic biomarkers were measured in androgen deprivation therapy–treated and control groups of men with prostate cancer. Significantly higher concentrations of some inflammatory biomarkers were found in the treatment group.