Tumor immune and glycan biomarkers for progressive prostate cancer

摘要 前列腺特异性抗原（PSA）筛查是用于前列腺癌检测的已建立且有用的工具， 然而，它在诊断时没有预测预后价值。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，患者是否应该接受侵入性干预或 作为“守株待兔”的主动监视来管理。因此，惰性前列腺癌患者可以 不必要的过度治疗;或者相反，患有侵袭性前列腺癌的患者可能会错过 需要的治疗，最终导致死亡。因此，迫切需要开发 局部前列腺癌的预后生物标志物，以指导临床决策， 每一个病人。本建议的目的是通过开发和 验证一组潜在的前列腺癌预后生物标志物。根据文献和我们的 令人信服的初步发现，我们假设血清中可溶性NKG 2D配体MIC（sMIC）水平在 与肿瘤相关聚糖谱的组合可以提供前列腺的预测生物标志物能力， 癌症预后我们收集了大量的前列腺癌组织和匹配的血清， 在前列腺切除术时被诊断患有局限性前列腺癌的男性。这些样品具有 注释的临床信息，包括随访PSA生化复发（BCR）状态。这些样品 将用于开发一组独特的预后生物标志物，并验证其特异性和敏感性。 将使用来自临床定义的前列腺的血清样本的独立队列进一步验证结果。 癌症患者。有四个具体目的：1）确定组织MIC的灵敏度和特异性， 血清sMIC预测BCR的敏感性和特异性; 2）确定组织和血清多药耐药的敏感性和特异性。 岩藻糖基化聚糖组在预测BCR中的作用; 3）确定血清和组织中的预测能力 生物标志物组4）鉴定的血清生物标志物组的预后能力， 患者样本的队列。拟议的研究将通过由一个 一个由资深调查员组成的团队。

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.