title: Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy.
abstract: The identification and development of biomarkers which predict response of muscle invasive bladder cancer (MIBC) patients to neoadjuvant chemotherapy would likely increase usage of this treatment option and thereby improve patient survival rates. MiRNA array and qRT-PCR validation was used to identify miRNA which are associated with response to neoadjuvant chemotherapy. RNA was extracted from a total of 41 archival, fully annotated, MIBC patient diagnostic biopsies (20 chemo-responders and 21 non-responders (response is defined as > 5 year survival rate and being pT0 post-chemotherapy)). Microarray and qPCR identified let-7c as being differentially expressed in chemo-responder versus non-responder patients. Patients with higher let-7c expression levels had significantly higher odds of responding to chemotherapy (p = 0.023, OR 2.493, 95% CI 1.121, 5.546), and assessment of let-7c levels allowed for prediction of patient response (AUC 0.72, positive predictive value 59%). Decreased let-7c was associated with MIBC incidence (p < 0.001), and significantly correlated with other related miRNA including those that were not differentially expressed between responders and non-responders. The combined data indicate let-7c plays a role in mediating chemoresistance to neoadjuvant chemotherapy in MIBC patients, and is a modest, yet clinically meaningful, predictor of patient response.
authors.affiliation: Department of Urology, University of California, Davis, School of Medicine and Comprehensive Cancer Center, Sacramento, California, USA; Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine and Comprehensive Cancer Center, Sacramento, California, USA; California Northstate University College of Pharmacy, Elk Grove, CA, USA.
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Vinall
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine and Comprehensive Cancer Center, Sacramento, California, USA.
authors.forename: Clifford G
authors.initials: CG
authors.lastname: Tepper
authors.affiliation: Department of Urology, University of California, Davis, School of Medicine and Comprehensive Cancer Center, Sacramento, California, USA.
authors.forename: Alexandra A Z
authors.initials: AA
authors.lastname: Ripoll
authors.affiliation: Department of Pathology, University of California, Davis, School of Medicine and Comprehensive Cancer Center, Sacramento, California, USA.
authors.forename: Regina F
authors.initials: RF
authors.lastname: Gandour-Edwards
authors.affiliation: Department of Public Health Sciences, University of California Davis, Davis, California, USA.
authors.forename: Blythe P
authors.initials: BP
authors.lastname: Durbin-Johnson
authors.affiliation: Department of Urology, University of California, Davis, School of Medicine and Comprehensive Cancer Center, Sacramento, California, USA.
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Yap
authors.affiliation: Department of Urology, University of California, Davis, School of Medicine and Comprehensive Cancer Center, Sacramento, California, USA; Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine and Comprehensive Cancer Center, Sacramento, California, USA; VA Northern California Health Care System, Mather, CA, USA.
authors.forename: Paramita M
authors.initials: PM
authors.lastname: Ghosh
authors.affiliation: Department of Urology, University of California, Davis, School of Medicine and Comprehensive Cancer Center, Sacramento, California, USA.
authors.forename: Ralph W
authors.initials: RW
authors.lastname: deVere White
keywords: chemoresistance; let-7c; miRNA; muscle invasive bladder cancer; neoadjuvant chemotherapy