Proteins provide an early warning of bladder cancer

Blood-based protein test could help with diagnosis and treatment

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Proteins in the bloodstream could help doctors detect bladder cancer at its earliest stages, according to a KAIMRC-led study. These findings lay the groundwork for a cheap and simple test to diagnose bladder cancer before it spreads and becomes harder to treat.

“Several biomarkers have been proposed for the detection and surveillance of bladder cancer, but unfortunately none of them warrant replacing the old system,” says Taoufik Nedjadi, a tumour biologist who led the study. The current test involves inserting a thin instrument with a camera at its tip into the bladder to visually examine the inside of the organ. Urine samples are also inspected under the microscope to see if they contain cancerous cells.

Both techniques have drawbacks — the former is invasive, while the latter often lacks accuracy. In contrast, the new blood-based protein signature holds immense promise as a reliable, non-invasive alternative. 

To identify the proteins involved in cancer formation and progression, Nedjadi and his colleagues analysed blood taken from a small group of Saudi patients diagnosed with low-grade non muscle invasive bladder cancer (NMIBC). They compared the protein levels with those in blood from healthy individuals and discovered a total of 15 proteins with significantly different expression patterns. Of these, 12 were more abundant in the patients, and three were less abundant.

The researchers focused on the three proteins with the starkest expression differences and validated their findings in an independent cohort of patients. All three proteins could be used to successfully diagnose cancer, but one in particular — a liver protein called haptoglobin — proved especially useful, with high sensitivity and specificity for discriminating between patients with early-stage bladder cancer and healthy individuals.

Haptoglobin is known to bind iron-carrying molecules in the bloodstream and prevent their loss through urine. The link between haptoglobin and bladder cancer remains a mystery, but Nedjadi’s team is working to clarify it through further experiments. His group is also studying other putative protein biomarkers that seem to be involved in regulating inflammatory responses, DNA replication, and other biological processes implicated in cancer development.

Nedjadi notes that these findings are only preliminary, based on analyses from only a few dozen patient samples. “To make this diagnostic tool a clinical reality, there is an urgent need to validate the recently discovered biomarkers in well-designed, multicentre clinical studies,” he says.

References

  1. Nedjadi, T., Benabdelkamal, H., Albarakati, N., Masood, A., Al-Sayyad, A. et al. Circulating proteomic signature for detection of biomarkers in bladder cancer patients. Scientific Reports 10, 10999 (2020). | article

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