Continuous culture of urine-derived bladder cancer cells for precision medicine

OBJECTIVE To determine if we could apply conditional reprogramming(CR) technique to generate continuous cell cultures from bladder cancer patients' urine and test the efficacies of drugs for personalized medicine. METHODS Urine and tumor samples were collected before clinical chemo-therapeutic treatment.The overall success rate was summarized. The origin and authentication of CR cultures(CRCs) was identified by immunostaining and short tandem repeat(STR) analysis.Single nucleotide variants(SNVs) and insertions-deletions(indels) were detected using whole-exome sequencing(WES). Dose-response measurements were used to generate drug sensitivity scores using R-statistical language.RESULTS The overall success rate of establishing urine CRCs was 83.3%(50/60), with 85.4%(41/48) of high grade bladder cancer, 75.0%(9/12) of low grade bladder cancer, and none(0/7) of the control group. Urine CRCs preserve the molecular characteristics and genetic alterations of the original tumors. Drug sensitivities of urine CRCs to oncology drugs varied among different patients and consisted with the corresponding clinical responses.Several drugs exhibited the great sensitivity in most patient derived cells, in which bortezomib was one of the most promising anti-bladder cancer drugs. CONCLUSION We successful y generated continuous urine-derived cancer cell cultures, which may offer a rapid, accurate,and non-invasive method for predicting patients clinical response.