RNA-seq profiling identified a three-lncRNA panel in serum as potential biomarker for muscle-invasive bladder cancer.

Abstract

Background: Preoperative determination of muscular infiltration is crucial for appropriate treatment planning in patients with muscle-invasive bladder cancer (MIBC). We aimed to explore early diagnostic biomarkers in serum for MIBC in this study.

Methods: The expression profiles of long noncoding RNA (lncRNA) were initially screened by high-throughput sequencing and evaluation of potential lncRNAs were conducted by two phases of RT-qPCR assays using serum samples from 190 patients with MIBC and 190 non-muscle-invasive BC (NMIBC) patients. Multivariate logistic regression analysis was applied to establish a diagnostic signature with high accuracy and Fagan's nomogram was plotted to promote clinical application. Bioinformatics analysis was used to determine the potential miRNA-mRNA binding of candidate lncRNAs.

Results: We identified three differentially expressed lncRNAs (LINC00565, LINC00592 and NDUFA6-AS1) and established a 3-lncRNA panel which demonstrated high diagnostic accuracy for MIBC with an AUC of 0.903 (95% CI: 0.850-0.942) and 0.875 (95% CI: 0.802-0.928) in the training and validation set. Moreover, construction and assessment of Fagan'nomogram demonstrated that the 3-lncRNA panel could exhibit practical and helpful values for clinical use. Finally, a network map based on LINC00565 was constructed and we found that the expression of miR-143-5p and miR-4516 were significantly correlated with LINC00565 in MIBC.

Conclusion: Our findings indicated that the constructed 3-lncRNA panel in serum showed favorable diagnostic capacity and might serve as promising non-invasive biomarkers in the early diagnosis of MIBC.