Aggressive Bladder Cancers May Be Identified by Measuring Two Urinary Proteins

British cancer researchers have found that measuring the urinary proteins epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) may represent a simple and useful approach for diagnosing and treating patients with the most aggressive bladder cancers.

Investigators at the University of Birmingham (United Kingdom) used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. This technique starts with the proteins in the mixture being digested, and the resulting peptides separated by liquid chromatography. Tandem mass spectrometry is then used to identify the peptides.

Data obtained by the shotgun proteomics procedure were compared with protein expression data from the Human Protein Atlas. EGFR was identified as a candidate biomarker and measured by ELISA in urine from 60 non-cancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up.

Results revealed that bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR was also detectable in urine and was highly elevated in some patients with high-grade bladder cancer. Urinary EGFR was an independent indicator of poor bladder cancer-specific survival. In multivariable models including both urinary EGFR and EpCAM, both biomarkers were predictive of bladder cancer-specific survival and had prognostic value over and above that provided by standard clinical observations. Higher levels of the biomarkers correlated with more aggressive cases of cancer and those with poorest rate of survival.

Senior author Dr. Douglas Ward, a senior research fellow at the University of Birmingham, said, "There is an urgent need for prognostic biomarkers that could guide patient management. If such a test could be delivered, in a noninvasive way, it could make treatment much more efficient and that can only be a good thing."

The study was published in the February 26, 2015, online edition of the British Journal of Cancer.

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