Abstract 145P
Background
For upper tract urinary carcinoma(UTUC) diagnosis, common clinical methods have some limitations. The imaging examinations need to be interpreted by experienced doctors and it is difficult to distinguish some soft lesions. Cytology and FISH are non-invasive but display low sensitivity. The use of ureteroscopy and biopsy may cause the recurrence of bladder tumors. These factors make the clinically urgent need for a sensitive and non-invasive method for the diagnosis of UTUC. Some urine liquid biopsy methods have been used, especially gene methylation research, but these studies have not achieved good sensitivity or specificity.
Methods
In this study, 170 hematuria patients were enrolled, among which, 76 were pathologically confirmed with UTUC while 94 with benign urinary diseases. Urine samples were collected before surgery and DNA was extracted from the pellet. A methylation-specific polymerase chain reaction assay was designed to detect CpG-sites on the ONECUT2 gene by bisulfite-specific real-time PCR. Ct values represent the relative quantity of methylated and unmethylated parts were measured by FAM and VIC signals separately, and the delta ct values were calculated as methylation score.
Results
Among the 170 urine samples, 159 were qualified for analysis. Based on the methylation score of each sample, when we took a cutoff of 7.93, the ONECUT2 methylation detection ability was the largest which displayed the AUC of 0.92. Thinking about the ONECUT2 methylation test solely at this cutoff value, we were able to detect genetic abnormalities in 82.9%(58/70) of UTUC+ samples and 6.7%(6/89) of UTUC- group. The ONECUT2 methylation assay demonstrated a sensitivity of 82.9%, a specificity of 93.3%, a positive predictive value (PPV) of 90.6% and a negative predictive value(NPV) of 87.4% in this cohort.
Conclusions
As so far, this is the first time to evaluate the ONECUT2 methylation in UTUC diagnosis. Its high sensitivity, high specificity, and non-invasiveness make it a potential clinical alternative. Further validation in a large prospective cohort of wide population is necessary to prove the true clinical value of this newly developed method.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hongzhao Li.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.