BACKGROUND: The noninvasive detection of RNA tumor markers in body fluids represents an attractive diagnostic option, but diagnostic performance of tissue-derived markers is often poorer when measured in body fluids rather than in tumors. We aimed to develop a procedure for measurement of tumor RNA in urine that would minimize donor-dependent influences on the results. METHODS: RNA isolated from urinary cell pellet, cell-depleted fraction, and whole urine was quantified by reverse transcription quantitative-PCR. The donor-dependent influence of urine background on individual steps of the standardized procedure was analyzed using an external RNA standard. Using a test set of samples from 61 patients with bladder cancer and 37 healthy donors, we compared 4 putative RNA tumor markers identified in whole urine with 5 established, tissue-derived RNA tumor markers for the detection of bladder cancer. RESULTS: Of the markers analyzed by this system, the RNA ratio of v-ets erythroblastosis virus E26 oncogene homolog 2 (avian; ETS2) to urokinase plasminogen activator (uPA) enabled the most specific (100%) and sensitive (75.4%) detection of bladder cancer from whole urine, with an area under the curve of 0.929 (95% CI 0.882-0.976). CONCLUSIONS: The described methodology for RNA marker detection in urine appears to be clinically applicable. The ratio of ETS2 mRNA to uPA mRNA in urine is a potential marker for bladder cancer.
BACKGROUND: The noninvasive detection of RNA tumor markers in body fluids represents an attractive diagnostic option, but diagnostic performance of tissue-derived markers is often poorer when measured in body fluids rather than in tumors. We aimed to develop a procedure for measurement of tumor RNA in urine that would minimize donor-dependent influences on the results. METHODS: RNA isolated from urinary cell pellet, cell-depleted fraction, and whole urine was quantified by reverse transcription quantitative-PCR. The donor-dependent influence of urine background on individual steps of the standardized procedure was analyzed using an external RNA standard. Using a test set of samples from 61 patients with bladder cancer and 37 healthy donors, we compared 4 putative RNA tumor markers identified in whole urine with 5 established, tissue-derived RNA tumor markers for the detection of bladder cancer. RESULTS: Of the markers analyzed by this system, the RNA ratio of v-ets erythroblastosis virus E26 oncogene homolog 2 (avian; ETS2) to urokinase plasminogen activator (uPA) enabled the most specific (100%) and sensitive (75.4%) detection of bladder cancer from whole urine, with an area under the curve of 0.929 (95% CI 0.882-0.976). CONCLUSIONS: The described methodology for RNA marker detection in urine appears to be clinically applicable. The ratio of ETS2 mRNA to uPA mRNA in urine is a potential marker for bladder cancer.
Authors: Ettickan Boopathi; Cristiano Mendes Gomes; Robert Goldfarb; Mary John; Vittala Gopal Srinivasan; Jaber Alanzi; S Bruce Malkowicz; Hasmeena Kathuria; Stephen A Zderic; Alan J Wein; Samuel Chacko Journal: Am J Pathol Date: 2011-05 Impact factor: 4.307
Authors: Li-Mei Chen; Myron Chang; Yunfeng Dai; Karl X Chai; Lars Dyrskjøt; Marta Sanchez-Carbayo; Tibor Szarvas; Ellen C Zwarthoff; Vinata Lokeshwar; Carmen Jeronimo; Alexander S Parker; Shanti Ross; Michael Borre; Torben F Orntoft; Tobias Jaeger; Willemien Beukers; Luis E Lopez; Rui Henrique; Paul R Young; Virginia Urquidi; Steve Goodison; Charles J Rosser Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-06-11 Impact factor: 4.254
Authors: Sijia Huang; Lei Kou; Hideki Furuya; Changhong Yu; Steve Goodison; Michael W Kattan; Lana Garmire; Charles J Rosser Journal: Cancer Epidemiol Biomarkers Prev Date: 2016-07-06 Impact factor: 4.254