PMID- 28418894 OWN - NLM STAT- MEDLINE DCOM- 20180402 LR - 20181113 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 25 DP - 2017 Jun 20 TI - Urinary RKIP/p-RKIP is a potential diagnostic and prognostic marker of clear cell renal cell carcinoma. PG - 40412-40424 LID - 10.18632/oncotarget.16341 [doi] AB - Clear cell Renal Cell Carcinoma (ccRCC) causes over 13,000 deaths each year, and about 20,000 new cases/year in Europe. In most cases, the causes are unknown and, most importantly, there are no reliable biomarkers for the diagnosis and prognosis of this disease. The search for sensitive biomarkers for early diagnosis and prognosis of clear cell Renal Cell Carcinoma (ccRCC) is currently a fast growing field. We carried out proteomics analysis of 93 urinary samples of healthy subjects (HS) and patients affected by ccRCC, prostate cancer (PCa) and chronic kidney disease (CKD), that was able to successfully distinguish each group.The most significant candidate biomarker was identified by mass spectrometry as Raf Kinase Inhibitor Protein (RKIP), a key regulator of cell signaling, already described in several cancer types as a metastasis suppressor. By combining ELISA, immunoblotting and tissue microarray, we demonstrated that, in ccRCC, urinary excretion of RKIP and its phosphorylated form (p-RKIP) reflected the tissue expression of these putative biomarkers. Baseline urinary RKIP, evaluated in an independent cohort of 56 ccRCC patients and 28 HS, successfully distinguished both groups and, most importantly, a cut-off value of 10 ng/mg/g Pr/uCr enabled a highly accurate prediction of Cancer-specific survival and Progression-free survival. Furthermore, p-RKIP was totally undetectable in both tissue and urine samples of ccRCC, showing a great potential for diagnostics purposes.Our data indicate that urinary RKIP encompasses both the unphosphorylated and the phosphorylated form and that their combined evaluation can help in the diagnosis and prognosis of ccRCC. FAU - Papale, Massimo AU - Papale M AD - Molecular Medicine Center, Section of Clinical Pathology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. AD - Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. FAU - Vocino, Grazia AU - Vocino G AD - Molecular Medicine Center, Section of Clinical Pathology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. FAU - Lucarelli, Giuseppe AU - Lucarelli G AD - Division of Urology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. FAU - Rutigliano, Monica AU - Rutigliano M AD - Division of Urology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. FAU - Gigante, Margherita AU - Gigante M AD - Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. FAU - Rocchetti, Maria Teresa AU - Rocchetti MT AD - Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. FAU - Pesce, Francesco AU - Pesce F AD - Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. FAU - Sanguedolce, Francesca AU - Sanguedolce F AD - Department of Pathology, University of Foggia, Foggia, Italy. FAU - Bufo, Pantaleo AU - Bufo P AD - Department of Pathology, University of Foggia, Foggia, Italy. FAU - Battaglia, Michele AU - Battaglia M AD - Division of Urology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. FAU - Stallone, Giovanni AU - Stallone G AD - Division of Nephrology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. FAU - Grandaliano, Giuseppe AU - Grandaliano G AD - Division of Nephrology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. FAU - Carrieri, Giuseppe AU - Carrieri G AD - Division of Urology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. FAU - Gesualdo, Loreto AU - Gesualdo L AD - Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. FAU - Ranieri, Elena AU - Ranieri E AD - Molecular Medicine Center, Section of Clinical Pathology, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Biomarkers, Tumor) RN - 0 (PEBP1 protein, human) RN - 0 (Phosphatidylethanolamine Binding Protein) SB - IM MH - Adult MH - Biomarkers, Tumor/metabolism/urine MH - Carcinoma, Renal Cell/*diagnosis/pathology/*urine MH - Disease-Free Survival MH - Enzyme-Linked Immunosorbent Assay MH - Europe MH - Humans MH - Kaplan-Meier Estimate MH - Kidney Neoplasms/*diagnosis/pathology/*urine MH - Phosphatidylethanolamine Binding Protein/metabolism/*urine MH - Phosphorylation MH - Renal Insufficiency, Chronic/diagnosis/*urine MH - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MH - Tissue Array Analysis PMC - PMC5522321 OTO - NOTNLM OT - RKIP OT - biomarkers OT - clear cell renal cell carcinoma OT - phospho-RKIP OT - urine COIS- CONFLICTS OF INTEREST Massimo Papale and Elena Ranieri are currently shareholders of FLUIDIA srl a biotech startup that submitted a patent application for a new method of RKIP/p-RKIP measurement in biological samples. (Applicant FLUIDIA srl; Inventor: Massimo Papale). EDAT- 2017/04/19 06:00 MHDA- 2018/04/03 06:00 PMCR- 2017/06/20 CRDT- 2017/04/19 06:00 PHST- 2016/09/13 00:00 [received] PHST- 2017/02/21 00:00 [accepted] PHST- 2017/04/19 06:00 [pubmed] PHST- 2018/04/03 06:00 [medline] PHST- 2017/04/19 06:00 [entrez] PHST- 2017/06/20 00:00 [pmc-release] AID - 16341 [pii] AID - 10.18632/oncotarget.16341 [doi] PST - ppublish SO - Oncotarget. 2017 Jun 20;8(25):40412-40424. doi: 10.18632/oncotarget.16341.