title: Combined serum and EPS-urine proteomic analysis using iTRAQ technology for discovery of potential prostate cancer biomarkers.
abstract: Prostate cancer (PCa) is one of the most common malignant tumors and a major cause of cancer-related death for men worldwide. The aim of our study was to identify potential non-invasive serum and expressed prostatic secretion (EPS)-urine biomarkers for accurate diagnosis of PCa. Here, we performed a combined isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to compare protein profiles using pooled serum and EPS-urine samples from 4 groups of patients: benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), localized PCa and metastatic PCa. The differentially expressed proteins were rigorously selected and further validated in a large and independent cohort using classical ELISA and Western blot assays. Finally, we established a multiplex biomarker panel consisting of 3 proteins (serum PF4V1, PSA, and urinary CRISP3) with an excellent diagnostic capacity to differentiate PCa from BPH [area under the receiver operating characteristic curve (AUC) of 0.941], which showed an evidently greater discriminatory ability than PSA alone (AUC, 0.757) (P<0.001). Importantly, even when PSA level was in the gray zone (4-10 ng/mL), a combination of PF4V1 and CRISP3 could achieve a relatively high diagnostic efficacy (AUC, 0.895). Furthermore, their combination also had the potential to distinguish PCa from HGPIN (AUC, 0.934). Our results demonstrated that the combined application of serum and EPS-urine biomarkers can improve the diagnosis of PCa and provide a new prospect for non-invasive PCa detection.
authors.affiliation: Urology Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Ultrasound Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Lizhu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Ultrasound Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Pathology Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Urology Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Shan
authors.affiliation: Urology Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yin
authors.affiliation: Urology Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Fei
authors.affiliation: Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Miao
authors.affiliation: Urology Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Song
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000652:urine*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000097:blood / Q000652:urine; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000652:urine; D012471:Salivary Proteins and Peptides / Q000097:blood / Q000652:urine; D029589:Seminal Plasma Proteins / Q000097:blood / Q000652:urine; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C489926:CRISP3 protein, human; C064936:PF4V1 protein, human; D012471:Salivary Proteins and Peptides; D029589:Seminal Plasma Proteins; D010978:Platelet Factor 4