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.

摘要

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

Plasma cells are enriched in localized prostate cancer in Black men and are associated with improved outcomes.

• DOI: 10.1038/s41467-021-21245-w
• 发表时间: 2021-02-10
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Weiner AB;Vidotto T;Liu Y;Mendes AA;Salles DC;Faisal FA;Murali S;McFarlane M;Imada EL;Zhao X;Li Z;Davicioni E;Marchionni L;Chinnaiyan AM;Freedland SJ;Spratt DE;Wu JD;Lotan TL;Schaeffer EM
• 通讯作者: Schaeffer EM