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ORIGINAL ARTICLE
Year : 2014  |  Volume : 3  |  Issue : 1  |  Page : 72-79

New serum biomarkers for prostate cancer diagnosis


1 Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA
2 Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA
3 Department of Molecular and Cellular Biology, Roswell Park Cancer Institute; Department of Medicine, Division of Allergy/Immunology and Rheumatology, University at Buffalo, Buffalo, NY, USA
4 Department of Medicine, Division of Allergy/Immunology and Rheumatology, University at Buffalo, Buffalo, NY, USA
5 Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA
6 Department of Urologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA

Correspondence Address:
Kailash C Chadha
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY
USA
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Source of Support: This study was supported by the Alliance Foundation, RPCI (KCC); R21(CA113950) (KCC) and by Margaret Duffy and Robert Cameron Troup Memorial Fund for Cancer Research of Kaleida Health and the Kaleida Health Foundation (SAS). This work was also supported by grants from the National Cancer Institute (CA31946 and CA114725) to Cancer and Leukemia Group B (CALGB) (Monica M. Bertagnolli, M.D., Chair) and to the CALGB Statistical Center (Daniel J. Sargent, Ph.D., CA33601). CALGB, through its clinical trials infrastructure, contributed bio.specimens and linked clinical data for this project. All other aspects of the study, including study design, specimen analysis and bio.statistical analysis were conducted by the study authors and did not involve either the CALGB Genitourinary Committee or CALGB.affiliated biostatisticians., Conflict of Interest: None


DOI: 10.4103/2278-0513.125802

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Background: Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective: The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods: Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results: TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions: The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted.


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