Tumor Markers Reveal Lethality of Bladder Cancers

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.

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