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Cancer biomarkers: separating the wheat from the chaff

The means of diagnosing bladder cancer are proving to be insufficient. Researchers from the BIG are proposing a methodology to determine effective urinary biomarkers.

Published on 23 November 2017

In France, bladder cancer is the 4th most common cancer in men, after prostate, lung and colon-rectum cancers. In women, it ranks 12th, and its incidence continues to increase. After surgical removal of the primary tumor, a significant proportion of cancers recur within five years. Patients should therefore be followed up systematically for several years. Tools for diagnosing and monitoring bladder cancer include cytology, which suffers from low sensitivity, and cystoscopy, which is both invasive and costly.

The European project DECanBio has established a list of potential urinary biomarkers for bladder cancer using proteomic and transcriptomic screens. "The list is long, with hundreds of candidates", explains Christophe Masselon, a researcher at the BIG. "And because of the low power of the statistical tests used in these so-called 'high-throughput' preliminary studies, a non-negligible proportion of these biomarker candidates are false discoveries." Systematic evaluation of these candidates is the limiting step in developing biomarkers. This evaluation is performed via proteomic methods that use targeted mass spectrometry (SRM: Selected Reaction Monitoring), a highly sensitive and specific technique, although the results must be evaluated with caution.

In collaboration with the CNIO in Madrid, the Mondor Hospital in Créteil, the Institut Curie, and the CRP Santé in Luxembourg, a team from the BIG has developed an effective and robust approach to process large-scale SRM data. This has made it possible to drastically reduce the list of potential bladder cancer biomarkers. "We used data from a cohort of patients suspected of developing bladder cancer," explains the biologist. "This is particularly valuable because many of them, who were not found to have any cancer, did have confounding pathologies. This helped to refine our results and to separate the wheat from the chaff." Thus, six proteins were recognized as potential diagnostic biomarkers for an incident cancer (1st cancer), and ten proteins were recognized for the diagnosis of recurrence. Regarding the prognosis for a risk of progression, 50 proteins could be eligible for the incident cancer and 19 proteins for recurrence.

This methodology was the subject of a patent application filed with the manufacturer Polyquant. The latter is currently looking for industrial partners to further test these biomarkers of the future.

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