Background and Aim: Different urinary markers of transitional cell carcinoma (TCC) have been proposed. None of them, however, is approved by the international guidelines or used with scientific safety by urologists in their clinical practice. Cystoscopy continues to represent the gold standard method of diagnosis, and is highly accurate, sensitive and specific. The urine cytology is instead non-invasive but has a high rate of false negative, especially in low-grade TCC. We try to give a significant answer of these open questions using a proteomic approach, that is widely used in molecular oncology. Using proteomic approaches, we previously demonstrated (1) that the levels of Tyr-phosphorylated proteins (TPPs) are highly increased in bladder cancer tissues and that soluble TPPs can be also detected in patient urine samples. Now, we have evaluated their diagnostic performances measuring urinary TPP levels in 230 urine samples from bladder cancer patients and healthy subjects. Patients and Methods: Patients with suspected bladder cancer were enrolled in this study before undergoing transurethral resection of the bladder or radical cystectomy. Patients with a histological diagnosis different from bladder cancer or with a previous bladder cancer history were excluded. Urines for the control group were collected from healthy blood donors, after an interview, to exclude urological problems. Only volunteers more than 50 years old were enrolled. The urinary levels of TPPs were analyzed using an experimental diagnostic test (pYtest, provided by Nurex srl). The area under the ROC curve (AUC), sensitivity, specificity, positive and negative predictive values (PPV and PNV) were calculated using Bayes� theorem (MedCalc 11.3.3). Results: Urinary TPP levels from 87 bladder cancer patients (7 Tx, 47 Ta, 17 T1, 12 T2/3, 4 CIS) and from 143 healthy subjects were measured. The AUC was 0.875 with a 95% confidence interval of 0.8260.915. For the best cut-off value (261.26 standard units), a sensitivity of 80.46% and a specificity of 79.72 % were obtained. PPV and PNV were 70.1% and 87.7%, respectively. Conclusion: The proteomic approach is shown to be helpful uro-oncology too, not only toward understanding the molecular pathways of carcinogenesis, but also toward detection of possible markers in the urine samples. Preliminary evaluation confirms the excellent diagnostic performances of TPPs as bladder cancer marker. To confirm and validate the proteomic approach through the individualisation of TPPs with the pYtest we need to increase the enrolled patients within a multicenter study. Next aim is to recruit more patients to confirm stastically the results a

Diagnostic validation of urinary tyr-phosphorylated proteins as bladder cancer marker

BATTAGLIA, Antonino;ALLASIA, MARCO;GONELLA, ANDREA;KHADJAVI, AMINA;NOTARPIETRO, AGATA;GIRIBALDI, Giuliana;TURRINI, Francesco Michelangelo;FONTANA, Dario;DESTEFANIS, Paolo Giuseppe;FREA, Bruno
2013

Abstract

Background and Aim: Different urinary markers of transitional cell carcinoma (TCC) have been proposed. None of them, however, is approved by the international guidelines or used with scientific safety by urologists in their clinical practice. Cystoscopy continues to represent the gold standard method of diagnosis, and is highly accurate, sensitive and specific. The urine cytology is instead non-invasive but has a high rate of false negative, especially in low-grade TCC. We try to give a significant answer of these open questions using a proteomic approach, that is widely used in molecular oncology. Using proteomic approaches, we previously demonstrated (1) that the levels of Tyr-phosphorylated proteins (TPPs) are highly increased in bladder cancer tissues and that soluble TPPs can be also detected in patient urine samples. Now, we have evaluated their diagnostic performances measuring urinary TPP levels in 230 urine samples from bladder cancer patients and healthy subjects. Patients and Methods: Patients with suspected bladder cancer were enrolled in this study before undergoing transurethral resection of the bladder or radical cystectomy. Patients with a histological diagnosis different from bladder cancer or with a previous bladder cancer history were excluded. Urines for the control group were collected from healthy blood donors, after an interview, to exclude urological problems. Only volunteers more than 50 years old were enrolled. The urinary levels of TPPs were analyzed using an experimental diagnostic test (pYtest, provided by Nurex srl). The area under the ROC curve (AUC), sensitivity, specificity, positive and negative predictive values (PPV and PNV) were calculated using Bayes� theorem (MedCalc 11.3.3). Results: Urinary TPP levels from 87 bladder cancer patients (7 Tx, 47 Ta, 17 T1, 12 T2/3, 4 CIS) and from 143 healthy subjects were measured. The AUC was 0.875 with a 95% confidence interval of 0.8260.915. For the best cut-off value (261.26 standard units), a sensitivity of 80.46% and a specificity of 79.72 % were obtained. PPV and PNV were 70.1% and 87.7%, respectively. Conclusion: The proteomic approach is shown to be helpful uro-oncology too, not only toward understanding the molecular pathways of carcinogenesis, but also toward detection of possible markers in the urine samples. Preliminary evaluation confirms the excellent diagnostic performances of TPPs as bladder cancer marker. To confirm and validate the proteomic approach through the individualisation of TPPs with the pYtest we need to increase the enrolled patients within a multicenter study. Next aim is to recruit more patients to confirm stastically the results a
Congresso Società Italiana di Urologia Oncologica SIURO
Firenze
9-11 giugno 2013
33
2316
2317
bladder cancer; biomarker
Antonino, Battaglia; Marco, Allasia; Andrea, Gonella; Amina, Khadjavi; Agata, Notarpietro; Francesca, Mannu; Giuliana, Giribaldi; Franco, Turrini; Dario, Fontana; Paolo, Destefanis; Bruno, Frea.
File in questo prodotto:
File Dimensione Formato  
Tyr_siuro2013.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 94.41 kB
Formato Adobe PDF
94.41 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/154951
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact