Tumor immune and glycan biomarkers for progressive prostate cancer

进展性前列腺癌的肿瘤免疫和聚糖生物标志物

• 批准号: 10305592
• 负责人: Sarki A. Abdulkadir
• 金额: $ 55.29万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-04 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10305592
• 关键词: Address; Animals; Antigen-Antibody Complex; Area; Biochemical; Biological Assay; Biological Markers; Cancer Patient; Cancer Prognosis; Clinical; Collaborations; Diagnosis; Discipline; Disease; Drug or chemical Tissue Distribution; Early Diagnosis; Human; Immune; Immunologic Receptors; Indolent; Inflammatory; Intervention; Ligands; Literature; Malignant neoplasm of prostate; Mass Spectrum Analysis; Medical; Methods; Nature; Neoplasm Metastasis; PSA screening; Pathologist; Patient observation; Patients; Pattern; Polysaccharides; Process; Prognosis; Prognostic Marker; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Recurrence; Research Personnel; Residual Tumors; Resources; Role; Sampling; Scientist; Screening for Prostate Cancer; Sensitivity and Specificity; Serum; South Carolina; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Therapeutic; Time; Tissue imaging; Tissues; Tumor Debulking; Tumor-Derived; Tumor-infiltrating immune cells; Universities; base; biomarker discovery; biomarker panel; cancer biomarkers; clinical decision-making; clinically relevant; cohort; cost; detection sensitivity; experimental study; follow-up; mass spectrometric imaging; men; mortality; neutralizing monoclonal antibodies; novel; overtreatment; predictive marker; predictive panel; prognostic; prognostic value; prostate cancer progression; side effect; therapy resistant; tissue biomarkers; tool; tumor; tumor immunology; tumor microenvironment; tumor progression; validation studies

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.

抽象的 前列腺特异性抗原 (PSA) 筛查是前列腺癌检测的既定且有用的工具， 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，即患者是否应该接受侵入性干预或 作为“观察等待”主动监视进行管理。因此，惰性前列腺癌患者可以 受到不必要的过度治疗；或者相反，患有侵袭性前列腺癌的患者可能会错过 缺乏必要的治疗，最终导致死亡。因此，迫切需要开发 局限性前列腺癌的预后生物标志物可指导最有利于患者的临床决策 每个病人。该提案的目的是通过开发和解决迫在眉睫的临床需求 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，我们假设可溶性 NKG2D 配体 MIC (sMIC) 的血清水平 与肿瘤相关聚糖谱相结合可以提供前列腺的预测生物标志物能力 癌症预后。我们收集了大量前列腺癌组织和匹配血清 来自在前列腺切除术时诊断出患有局限性前列腺癌的男性。这些样本有 带注释的临床信息，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。 研究结果将通过临床定义的前列腺的独立血清样本队列得到进一步验证 癌症患者。有四个具体目标： 1) 确定组织 MIC 的敏感性和特异性，以及 血清 sMIC 预测 BCR； 2) 确定组织和血清多重检测的敏感性和特异性 预测 BCR 的岩藻糖基化聚糖组； 3) 确定血清和组织的预后能力 生物标志物组 4) 验证已识别的血清生物标志物组的预后能力，具有独立的 患者样本队列。拟议的研究将通过由以下人员领导的协作努力完成 完善的调查员团队。

项目成果

NKG2D and its ligands in cancer.

• DOI: 10.1016/j.coi.2018.02.004
• 发表时间: 2018-04
• 期刊: Current opinion in immunology
• 影响因子: 7
• 作者: Dhar P;Wu JD
• 通讯作者: Wu JD

Association between inflammatory bowel disease and prostate cancer: A large-scale, prospective, population-based study.

• DOI: 10.1002/ijc.33048
• 发表时间: 2020-11-15
• 期刊: International journal of cancer
• 影响因子: 6.4
• 作者: Meyers TJ;Weiner AB;Graff RE;Desai AS;Cooley LF;Catalona WJ;Hanauer SB;Wu JD;Schaeffer EM;Abdulkadir SA;Kundu SD;Witte JS
• 通讯作者: Witte JS

The Human Soluble NKG2D Ligand Differentially Impacts Tumorigenicity and Progression in Temporal and Model-Dependent Modes.

• DOI: 10.3390/biomedicines12010196
• 发表时间: 2024-01-16
• 期刊: BIOMEDICINES
• 影响因子: 4.7
• 作者: Serritella, Anthony V.;Saenz-Lopez Larrocha, Pablo;Dhar, Payal;Liu, Sizhe;Medd, Milan M.;Jia, Shengxian;Cao, Qi;Wu, Jennifer D.
• 通讯作者: Wu, Jennifer D.

Could Harnessing Natural Killer Cell Activity Be a Promising Therapy for Prostate Cancer?

• DOI: 10.1615/critrevimmunol.2021037614
• 发表时间: 2021
• 期刊: Critical reviews in immunology
• 影响因子: 1.3
• 作者: Wu J

Glycan Imaging Mass Spectrometry: Progress in Developing Clinical Diagnostic Assays for Tissues, Biofluids, and Cells.

• DOI: 10.1016/j.cll.2021.03.005
• 发表时间: 2021-06
• 期刊: Clinics in laboratory medicine
• 影响因子: 1.7
• 作者: Blaschke CRK;McDowell CT;Black AP;Mehta AS;Angel PM;Drake RR
• 通讯作者: Drake RR