Tumor immune and glycan biomarkers for progressive prostate cancer

摘要 前列腺特异性抗原(PSA)筛查是前列腺癌检测的公认和有用的工具， 然而，它在诊断中没有预测预后的价值。对于早期诊断的局限性前列腺癌， 主要的临床挑战是治疗决策，即患者是否应该接受侵入性干预或 被管理为“警惕等待”的主动监视。因此，懒惰的前列腺癌患者可以 不必要地过度治疗；或者相反，侵袭性前列腺癌患者可能会错过 接受必要的治疗，这最终会导致死亡。因此，这是一个迫切需要发展的问题。 预测局限性前列腺癌预后的生物标志物用于指导临床决策 每一位病人。这项建议的目标是通过开发和开发 验证一组潜在的前列腺癌预后生物标记物。基于文献和我们的 令人信服的初步发现，我们假设血清中可溶性NKG2D配体MIC(SMIC)水平在 结合肿瘤相关的糖链图谱可以提供预测前列腺癌的生物标记物能力 癌症预后。我们收集了大量前列腺癌组织和相匹配的血清 来自前列腺摘除时被诊断为局限性前列腺癌的男性。这些样品有 注解的临床信息包括随访PSA生化复发(BCR)情况。这些样品 将被用来开发一组独特的预后生物标志物，并验证它们的特异性和敏感性。 研究结果将通过来自临床明确的前列腺的血清样本的独立队列进一步验证。 癌症患者。有四个具体目标：1)确定组织MIC和 血清SMIC预测bcr；2)测定组织和血清多项指标的敏感性和特异性。 岩藻糖化多糖板预测bcr；3)决定血清和组织的预后能力 生物标记物小组4)验证所识别的一组血清生物标志物的预后能力 病人样本的队列。拟议的研究将通过一个由 一队久负盛名的调查员。

Abstract Prostate specific antigen (PSA) screening is an established and useful tool for prostate cancer detection, however, it has no predictive prognostic value at diagnosis. For early diagnosed localized prostate cancer, the major clinical challenge is the treatment decision, in whether a patient should receive invasive intervention or be managed as “watchful waiting” active surveillance. Consequently, patients with indolent prostate cancer can be unnecessarily over-treated; or conversely, patients with prostate cancer of an aggressive nature may miss out on needed treatment, which ultimately leads to mortality. Therefore, it is an urgent need to develop prognostic biomarkers for localized prostate cancer to guide clinical decision making that is most beneficial to each patient. The objective of this proposal is to address the imminent clinical need by developing and validating a panel of potential prostate cancer prognostic biomarkers. Based on the literature and our compelling preliminary findings, we hypothesize that serum levels of the soluble NKG2D ligand MIC (sMIC) in combination with tumor-associated glycan profiles can provide the predictive biomarker capacity for prostate cancer prognosis. We have assembled large cohorts of prostate cancer tissues and matching serum collected from men diagnosed with localized prostate cancer at the time of prostatectomy. These samples have annotated clinical information including follow up PSA biochemical recurrence (BCR) status. These samples will be used to develop a unique panel of prognostic biomarkers and validate their specificity and sensitivity. Findings will be further validated with independent cohorts of serum samples from clinically-defined prostate cancer patients. There are four Specific Aims: 1) Determine the sensitivity and specificity of tissue MIC and serum sMIC in predicting BCR; 2) Determine the sensitivity and specificity of tissue and serum multi- fucosylated glycan panels in predicting BCR; 3) Determine the prognostic capacity of serum and tissue biomarker panel 4) Validate prognostic capacity of the identified panel of serum biomarkers with independent cohorts of patient samples. The proposed study will be accomplished through a collaborative effort led by a team of well-established investigators.