TY - JOUR
T1 - Use of quantitative shotgun proteomics to identify fibronectin 1 as a potential plasma biomarker for clear cell carcinoma of the kidney
AU - Yokomizo, Akira
AU - Takakura, Michiko
AU - Kanai, Yae
AU - Sakuma, Tomohiro
AU - Matsubara, Junichi
AU - Honda, Kazufumi
AU - Naito, Seiji
AU - Yamada, Tesshi
AU - Ono, Masaya
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2011
Y1 - 2011
N2 - Background: Early detection would be one of the most effective means to improve the outcome of renal cell carcinoma (RCC). We searched for a new plasma marker for RCC using a label-free quantitative shotgun proteomics method. Methods: Plasma proteins were digested by trypsin, and the resulting peptides were analyzed by 2-Dimensional Image Converted Analysis of Liquid chromatography mass spectrometry (2DICAL). An identified biomarker candidate was subjected to validation using the Amplified Luminescent Proximity Homogeneous Assay (AlphaLISA). Results: Among a total of 23,407 independent MS peaks, we found that the mean intensity of 59~peaks significantly differed between 20 clear cell RCC patients and 20~healthy controls. MS/MS spectra from 16 of the 59~peaks matched the amino acid sequences of the fibronectin 1 (FN1) gene product. {The increased plasma level of FN1 in RCC patients was validated in a cohort of in 77 patients and 130 healthy controls (p<0.0001).} Conclusions: The FN1 is considered to be a promising biomarker candidate for clear cell RCC. Furthermore, AlphaLISA is an alternate to the conventional enzyme-linked immunosorbent assay and should prove useful for the rapid validation of biomarker candidates.
AB - Background: Early detection would be one of the most effective means to improve the outcome of renal cell carcinoma (RCC). We searched for a new plasma marker for RCC using a label-free quantitative shotgun proteomics method. Methods: Plasma proteins were digested by trypsin, and the resulting peptides were analyzed by 2-Dimensional Image Converted Analysis of Liquid chromatography mass spectrometry (2DICAL). An identified biomarker candidate was subjected to validation using the Amplified Luminescent Proximity Homogeneous Assay (AlphaLISA). Results: Among a total of 23,407 independent MS peaks, we found that the mean intensity of 59~peaks significantly differed between 20 clear cell RCC patients and 20~healthy controls. MS/MS spectra from 16 of the 59~peaks matched the amino acid sequences of the fibronectin 1 (FN1) gene product. {The increased plasma level of FN1 in RCC patients was validated in a cohort of in 77 patients and 130 healthy controls (p<0.0001).} Conclusions: The FN1 is considered to be a promising biomarker candidate for clear cell RCC. Furthermore, AlphaLISA is an alternate to the conventional enzyme-linked immunosorbent assay and should prove useful for the rapid validation of biomarker candidates.
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U2 - 10.3233/CBM-2012-0243
DO - 10.3233/CBM-2012-0243
M3 - Article
C2 - 22674303
AN - SCOPUS:84862868775
VL - 10
SP - 175
EP - 183
JO - Cancer Biomarkers
JF - Cancer Biomarkers
SN - 1574-0153
IS - 3-4
ER -