BACKGROUND: No validated renal cell carcinoma (RCC) marker is known for detection of asymptomatic disease in selected populations or for prognostic purposes or treatment monitoring. We identified immunogenic proteins as tumor markers for RCC by combining conventional proteome analysis with serological screening, and we investigated the diagnostic clinical value of such markers in serum. METHODS: We studied the immunogenic protein expression profile of CAL 54, a human RCC cell line, by 2-dimensional electrophoresis combined with immunoblotting using sera from healthy donors compared with RCC patients. We developed a homogeneous, fluorescent, dual-monoclonal immunoassay for metalloproteinase 7 (MMP-7) and used it to measure MMP-7 in sera from 30 healthy donors, 30 RCC patients, and 40 control patients. RESULTS: Pro-MMP-7 (29 kDa; pI 7.7) in the CAL 54 cell line secretome was an immunogenic protein reactive with RCC patient sera but not with control sera. The concentrations of pro-MMP-7 were increased (P <0.0001) in sera of RCC patients (median 7.56 microg/L; range 3.12-30.5 microg/L) compared with healthy controls (median 2.13 microg/L; range 0.17-3.5 microg/L). Serum pro-MMP-7 had a sensitivity of 93% (95% CI 78%-99%) at a specificity of 75% (59%-87%) for RCC in the samples tested. CONCLUSION: Proteomics technology combined with serology led to the identification of serum pro-MMP-7 as a marker of RCC and represents a powerful tool in searching for candidate proteins as biomarkers.
BACKGROUND: No validated renal cell carcinoma (RCC) marker is known for detection of asymptomatic disease in selected populations or for prognostic purposes or treatment monitoring. We identified immunogenic proteins as tumor markers for RCC by combining conventional proteome analysis with serological screening, and we investigated the diagnostic clinical value of such markers in serum. METHODS: We studied the immunogenic protein expression profile of CAL 54, a humanRCC cell line, by 2-dimensional electrophoresis combined with immunoblotting using sera from healthy donors compared with RCCpatients. We developed a homogeneous, fluorescent, dual-monoclonal immunoassay for metalloproteinase 7 (MMP-7) and used it to measure MMP-7 in sera from 30 healthy donors, 30 RCCpatients, and 40 control patients. RESULTS: Pro-MMP-7 (29 kDa; pI 7.7) in the CAL 54 cell line secretome was an immunogenic protein reactive with RCCpatient sera but not with control sera. The concentrations of pro-MMP-7 were increased (P <0.0001) in sera of RCCpatients (median 7.56 microg/L; range 3.12-30.5 microg/L) compared with healthy controls (median 2.13 microg/L; range 0.17-3.5 microg/L). Serum pro-MMP-7 had a sensitivity of 93% (95% CI 78%-99%) at a specificity of 75% (59%-87%) for RCC in the samples tested. CONCLUSION: Proteomics technology combined with serology led to the identification of serum pro-MMP-7 as a marker of RCC and represents a powerful tool in searching for candidate proteins as biomarkers.
Authors: Ali Tüzün İnce; Kemal Yıldız; Venkatanarayana Gangarapu; Yusuf Kayar; Birol Baysal; Oğuzhan Karatepe; Ahu Sarbay Kemik; Hakan Şentürk Journal: Int J Clin Exp Med Date: 2015-02-15
Authors: Sam C Wang; Justin R Parekh; Matthew R Porembka; Hari Nathan; Michael I D'Angelica; Ronald P DeMatteo; Yuman Fong; T Peter Kingham; William R Jarnagin; Peter J Allen Journal: J Gastrointest Surg Date: 2016-02-26 Impact factor: 3.452
Authors: Egbert Oosterwijk; W Kimryn Rathmell; Kerstin Junker; A Rose Brannon; Frédéric Pouliot; David S Finley; Peter F A Mulders; Ziya Kirkali; Hirotsugo Uemura; Arie Belldegrun Journal: Eur Urol Date: 2011-07-05 Impact factor: 20.096
Authors: Christian Niedworok; Frank vom Dorp; Stephan Tschirdewahn; Herbert Rübben; Henning Reis; Miklos Szucs; Tibor Szarvas Journal: Int Urol Nephrol Date: 2016-01-02 Impact factor: 2.370