Tumor size, stage and grade alterations of urinary peptidome in RCC.
BACKGROUND
Several promising biomarkers have been found for RCC, but none of them has been used in clinical practice for predicting tumour progression. The most widely used features for predicting tumour aggressiveness still remain the cancer stage, size and grade. Therefore, the aim of our study is to investigate the urinary peptidome to search and identify peptides whose concentrations in urine are linked to tumour growth measure and clinical data.


METHODS
A proteomic approach applied to ccRCC urinary peptidome (n = 117) based on prefractionation with activated magnetic beads followed by MALDI-TOF profiling was used. A systematic correlation study was performed on urinary peptide profiles obtained from MS analysis. Peptide identity was obtained by LC-ESI-MS/MS.


RESULTS
Fifteen, twenty-six and five peptides showed a statistically significant alteration of their urinary concentration according to tumour size, pT and grade, respectively. Furthermore, 15 and 9 signals were observed to have urinary levels statistically modified in patients at different pT or grade values, even at very early stages. Among them, C1RL, A1AGx, ZAG2G, PGBM, MMP23, GP162, ADA19, G3P, RSPH3, DREB, NOTC2 SAFB2 and CC168 were identified.


CONCLUSIONS
We identified several peptides whose urinary abundance varied according to tumour size, stage and grade. Among them, several play a possible role in tumorigenesis, progression and aggressiveness. These results could be a useful starting point for future studies aimed at verifying their possible use in the managements of RCC patients.
Department of Health Science, School of Medicine, University of Milano-Bicocca (UNIMIB), Via Cadore, 48, 20900, Monza, Italy. clizia.chinello@unimib.it.
Clizia
C
Chinello
Department of Health Science, School of Medicine, University of Milano-Bicocca (UNIMIB), Via Cadore, 48, 20900, Monza, Italy. m.cazzaniga15@campus.unimib.it.
Marta
M
Cazzaniga
Department of Health Science, School of Medicine, University of Milano-Bicocca (UNIMIB), Via Cadore, 48, 20900, Monza, Italy. g.desio@campus.unimib.it.
Gabriele
G
De Sio
Department of Health Science, School of Medicine, University of Milano-Bicocca (UNIMIB), Via Cadore, 48, 20900, Monza, Italy. andyjamessmith6@hotmail.com.
Andrew James
AJ
Smith
Urology Unit, Department of Specialistic Surgical Sciences, Ospedale Maggiore Policlinico Foundation, Milan, Italy. angelica_grasso@yahoo.it.
Angelica
A
Grasso
Urology Unit, Department of Specialistic Surgical Sciences, Ospedale Maggiore Policlinico Foundation, Milan, Italy. bernardo.rocco@gmail.com.
Bernardo
B
Rocco
Department of Laboratory Medicine, Hospital of Desio, Desio, Italy. stefano.signorini@unimib.it.
Stefano
S
Signorini
Department of Surgical Pathology, Cytology, Medical Genetics and Nephropathology, Azienda Ospedaliera San Gerardo, Monza, Italy. m.grasso@hsgerardo.org.
Marco
M
Grasso
Department of Medicine, Surgery and Dental Sciences, Pathology Unit, IRCCS-Policlinico Foundation, Mangiagalli and Regina Elena, University of Milan, Milan, Italy. silvano.bosari@unimi.it.
Silvano
S
Bosari
Department of Informatics, Systems and Communication, University of Milano-Bicocca, Milan, Italy. zoppis@disco.unimib.it.
Italo
I
Zoppis
Department of Informatics, Systems and Communication, University of Milano-Bicocca, Milan, Italy. giancarlo.mauri@unimib.it.
Giancarlo
G
Mauri
Department of Health Science, School of Medicine, University of Milano-Bicocca (UNIMIB), Via Cadore, 48, 20900, Monza, Italy. fulvio.magni@unimib.it.
Fulvio
F
Magni
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000652:urine*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010455:Peptides / Q000737:chemistry / Q000652:urine*; D040901:Proteomics; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
D014408:Biomarkers, Tumor; D010455:Peptides