4.5 Review

Proteomic discovery of non-invasive biomarkers of localized prostate cancer using mass spectrometry

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NATURE REVIEWS UROLOGY
卷 18, 期 12, 页码 707-724

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NATURE PORTFOLIO
DOI: 10.1038/s41585-021-00500-1

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资金

  1. National Cancer Institute Early Detection Research Network [1U01CA214194-01]
  2. Prostate Cancer Canada [400398]
  3. Canadian Cancer Society Impact Grant [705649]
  4. Ontario Graduate Scholarship
  5. Paul STARITA Graduate Student Fellowship
  6. CIHR Vanier Award
  7. NIH/NCI [P30CA016042]

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Prostate cancer patients urgently need biomarkers to improve risk stratification, as current clinical prognostic tools are not accurate enough. Mass spectrometry technologies enable systematic discovery and validation of protein-based biomarkers in relevant fluids. Existing protein biomarkers for diagnosis, prognosis, and relapse-monitoring in localized prostate cancer are predominantly centered around PSA and its variants.
Biomarkers that can improve risk stratification of patients with prostate cancer are urgently needed. In this Review, Khoo et al. outline mass spectrometry technologies that enable the systematic discovery and targeted validation of protein-based biomarkers in prostate-associated fluids. Prostate cancer is the second most frequently diagnosed non-skin cancer in men worldwide. Patient outcomes are remarkably heterogeneous and the best existing clinical prognostic tools such as International Society of Urological Pathology Grade Group, pretreatment serum PSA concentration and T-category, do not accurately predict disease outcome for individual patients. Thus, patients newly diagnosed with prostate cancer are often overtreated or undertreated, reducing quality of life and increasing disease-specific mortality. Biomarkers that can improve the risk stratification of these patients are, therefore, urgently needed. The ideal biomarker in this setting will be non-invasive and affordable, enabling longitudinal evaluation of disease status. Prostatic secretions, urine and blood can be sources of biomarker discovery, validation and clinical implementation, and mass spectrometry can be used to detect and quantify proteins in these fluids. Protein biomarkers currently in use for diagnosis, prognosis and relapse-monitoring of localized prostate cancer in fluids remain centred around PSA and its variants, and opportunities exist for clinically validating novel and complimentary candidate protein biomarkers and deploying them into the clinic.

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