Urine analysis and protein networking identify met as a marker of metastatic prostate cancer

尿液分析和蛋白质网络鉴定出met是转移性前列腺癌的标志物

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作者:Andrea L Russo, Kimberly Jedlicka, Meredith Wernick, Debbie McNally, Melissa Kirk, Mary Sproull, Sharon Smith, Uma Shankavaram, Aradhana Kaushal, William D Figg, William Dahut, Deborah Citrin, Donald P Bottaro, Paul S Albert, Philip J Tofilon, Kevin Camphausen

Conclusion

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.

Purpose

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. Experimental design: 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.

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