Urine analysis and protein networking identify met as a marker of metastatic prostate cancer.
OBJECTIVE
Metastatic prostate cancer is a major cause of death of men in the United States. Expression of met, a receptor tyrosine kinase, has been associated with progression of prostate cancer.


METHODS
To investigate met as a biomarker of disease progression, urinary met was evaluated via ELISA in men with localized (n = 75) and metastatic (n = 81) prostate cancer. Boxplot analysis was used to compare the distribution of met values between each group. We estimated a receiver operating characteristic curve and the associated area under the curve to summarize the diagnostic accuracy of met for distinguishing between localized and metastatic disease. Protein-protein interaction networking via yeast two-hybrid technology supplemented by Ingenuity Pathway Analysis and Human Interactome was used to elucidate proteins and pathways related to met that may contribute to progression of disease.


RESULTS
Met distribution was significantly different between the metastatic group and the group with localized prostate cancer and people with no evidence of cancer (P < 0.0001). The area under the curve for localized and metastatic disease was 0.90, with a 95% confidence interval of 0.84 to 0.95. Yeast two-hybrid technology, Ingenuity Pathway Analysis, and Human Interactome identified 89 proteins that interact with met, of which 40 have previously been associated with metastatic prostate cancer.


CONCLUSIONS
Urinary met may provide a noninvasive biomarker indicative of metastatic prostate cancer and may be a central regulator of multiple pathways involved in prostate cancer progression.
Russo
Andrea L
AL
Radiation Oncology Branch, National Cancer Institute, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Jedlicka
Kimberly
K
Wernick
Meredith
M
McNally
Debbie
D
Kirk
Melissa
M
Sproull
Mary
M
Smith
Sharon
S
Shankavaram
Uma
U
Kaushal
Aradhana
A
Figg
William D
WD
Dahut
William
W
Citrin
Deborah
D
Bottaro
Donald P
DP
Albert
Paul S
PS
Tofilon
Philip J
PJ
Camphausen
Kevin
K
D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism / Q000502:physiology / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000652:urine*; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000502:physiology / Q000652:urine*; D019859:Proto-Oncogene Proteins c-met; D012372:ROC Curve; D017978:Receptors, Growth Factor / Q000032:analysis / Q000502:physiology; D014407:Tumor Cells, Cultured; D016482:Urinalysis / Q000379:methods*
D014408:Biomarkers, Tumor; D011506:Proteins; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met