NEW ORLEANS, LA USA (UroToday.com) - Due to the invasiveness of cystoscopy and the low sensitivity of cytology, a better test is needed for the diagnosis of bladder cancer. Dr. Mandy Sin presented one such modality that may have promise: linear discriminant analysis in a urine-based test. Her group has utilized an RT-PCR based, near-patient, on-demand test with high sensitivity and specificity. Known as GeneXpert®, this test is currently used for diagnosis of Chlamydia and gonorrhea, as well as other areas of oncology and genetics. It is preloaded with RT-PCR reagents for 6mRNA targets, with 5 target genes and 1 internal control. Results of the test are available within 90 minutes.
Ten mRNA markers were chosen for screening with literature support and confirmed RT-PRC performance in urine. These were used in a training set that was comprised of 444 urine samples from 18 sites. Clinically, 251 had negative cystoscopy, 42 had low-grade disease, 43 had high-grade, 64 had no cystoscopy (healthy), and 4 had UTI. mRNA expression was quantified with RT-PCR, and linear discriminant analysis was performed to find an optimal reduced linear combination of input variables that best separate two populations, cancer vs no cancer. The LDA equation with 10 markers was then reduced to the 5 best-performing markers: IGF2, ANAX10, CRH, UPK1B, and ABL1. An LDA cutoff value of 0.09 was selected to predict cancer vs no cancer.
The sensitivity of the 5-marker panel was 89% for cancer, 98% for high-grade disease, and 71% for low-grade disease. This outperformed cytology (sensitivities of 37%, 43%, and 17%, respectively) and FISH (75%, 93%, and 39%). Specificity among patients with hematuria was 82% in the 5-marker panel, vs 93% for cytology, and 74% for FISH.
A validation study was performed that took 252 samples from 7 sites, and the sensitivity and specificity findings of the training cohort were confirmed. Dr. Sin concluded that the 5-marker gene signature could provide accurate detection in 90 minutes, with performance characteristics that are better than those of cytology and FISH. Prospective studies with additional samples are in progress.
Presented by Lai Yi Mandy Sin at the American Urological Association (AUA) Annual Meeting - May 15 - 19, 2015 - New Orleans, LA USA
Stanford School of Medicine, Stanford, CA USA
Reported by Nikhil Waingankar, medical writer for UroToday.com