A Multiplex Test Assessing MiR663ame and VIMme in Urine Accurately Discriminates Bladder Cancer from Inflammatory Conditions

Abstract

Bladder cancer (BlCa) is a common malignancy with significant morbidity and mortality. Current diagnostic methods are invasive and costly, showing the need for newer biomarkers. Although several epigenetic-based biomarkers have been proposed, their ability to discriminate BlCa from common benign conditions of the urinary tract, especially inflammatory diseases, has not been adequately explored. Herein, we sought to determine whether VIMme and miR663ame might accurately discriminate those two conditions, using a multiplex test. Performance of VIMme and miR663ame in tissue samples and urines in testing set confirmed previous results (96.3% sensitivity, 88.2% specificity, area under de curve (AUC) 0.98 and 92.6% sensitivity, 75% specificity, AUC 0.83, respectively). In the validation sets, VIMme-miR663ame multiplex test in urine discriminated BlCa patients from healthy donors or patients with inflammatory conditions, with 87% sensitivity, 86% specificity and 80% sensitivity, 75% specificity, respectively. Furthermore, positive likelihood ratio (LR) of 2.41 and negative LR of 0.21 were also disclosed. Compared to urinary cytology, VIMme-miR663ame multiplex panel correctly detected 87% of the analysed cases, whereas cytology only forecasted 41%. Furthermore, high miR663ame independently predicted worse clinical outcome, especially in patients with invasive BlCa. We concluded that the implementation of this panel might better stratify patients for confirmatory, invasive examinations, ultimately improving the cost-effectiveness of BlCa diagnosis and management. Moreover, miR663ame analysis might provide relevant information for patient monitoring, identifying patients at higher risk for cancer progression.

Practicability of clinical application of bladder cancer molecular classification and additional value of epithelial-to-mesenchymal transition: prognostic value of vimentin expression

“…On the one hand, NMIBC is the most frequent BlCa phenotype [35], and disease recurrence is very frequent. Substantial research efforts have been put towards uncovering non-invasive, liquid biopsy-based biomarkers for accurately diagnosing and following-up these patients [36,37]. One major gap in NMIBC relates to patient prognostication and risk stratification after resection, fundamental for establishing the most appropriate follow-up strategy.…”

Vimentin epigenetic deregulation in Bladder Cancer associates with acquisition of invasive and metastatic phenotype through epithelial-to-mesenchymal transition

“…Urothelial cell carcinomas (UCCs) are the most common form of BlCa, arising along the urinary tract, mostly in the lower tract (bladder and urethra), but also in the Ivyspring International Publisher upper tract (renal pelvis and ureters) [3][4][5][6][7]. The gold-standard diagnostic techniques are mostly invasive and uncomfortable, which led us and others to develop non-invasive tests [8][9][10][11][12][13]. We have previously shown that a biomarker panel (VIM, GDF15 and TMEFF2 promoter methylation) accurately detected both lower and upper tract UCC in urine, and, more recently, that a multiplex panel (VIM and miR663a promoter methylation) accurately discriminated BlCa from inflammatory bladder conditions [8,9,11].…”

The Role of Novel Bladder Cancer Diagnostic and Surveillance Biomarkers—What Should a Urologist Really Know?

“…They found that it was able to diagnose BCa with 80% sensitivity and 88% specificity as well as differentiate low risk patients from healthy controls [ 46 ]. On the other hand, combining only miRNA663 and methylated VIM diagnostic values were slightly inferior, 92.6% sensitivity and 90% NPV [ 141 ].…”