Tumor Markers Reveal Lethality of Bladder Cancers

Bladder cancer is the fourth most common cause of cancer-related death among men in the USA and more than 75,000 new cases will be diagnosed this year and more than 16,000 people will die from this disease.

Tumor cells collected during the removal of a cancerous bladder and in some cases transplanted into mice with weakened immune systems could help physicians rapidly identify high-risk cancers, determine prognosis and refine the use of biomarkers to personalize care for patients with this common cancer.

Medical scientists at the University of Chicago Medical Center (Chicago, IL, USA) obtained tumor samples from 71 bladder cancer patients treated at the University and used flow cytometry to isolate and count specific subtypes of tumor cells in each sample. A portion of the tumor was separated for xenograft injection. The remaining tissue was disaggregated in Miltenyi gentleMACS tube tissue dissociator (Miltenyi Biotec, Bergisch Gladbach, Germany), then enzymatically treated using DNase and Liberase.

Single-cell suspensions of patient tumor tissue were stained using antibodies and flow cytometry was performed using the BD LSRFortessa and BD LSR-II and cells were sorted using BD FACSAriaIII. Flow sorted cells as well as samples of cells from the bulk tumor were collected and ribonucleic acid (RNA) was extracted and assayed in duplicate using Illumina HumanHT-12 v4 Expression BeadChip microarrays.

The team found that detection of poorly differentiated basal tumor cells (BTC) in early stage cancers; overexpression in those cells of a gene known as cell division cycle 25C, which plays a key role in the regulation of cell division; or the ability of tumor fragments to grow when transplanted into a mouse, all predicted an increased risk of death. Analyzing the global expression of genes in BTCs, they also identified a potentially prognostic biomarker for bladder cancer: cell division cycle 25C (CDC25C), a protein that drives cell division. An expanded analysis, including 400 bladder cancer patients, found that the expression of this protein is associated with an increased risk of death even after the removal of the cancerous bladder.

This association disappeared in patients who had previously received chemotherapy. A test for CDC25C could, the authors suggest, help determine whether a bladder cancer patient is likely to benefit from drug treatment. Ralph Weichselbaum, MD, a professor and senior author of the study said, “Prognostic knowledge can change a lot about how you choose to treat a cancer. We may be able to avoid aggressive measures if we find a tumor has relatively few basal cells, But if a bladder tumor has a lot of basal cells, we may need to take the entire bladder out and follow that with chemotherapy.” The study was published on October 24, 2016, in the journal Scientific Reports.

Related Links:
University of Chicago Medical Center
Miltenyi Biotec