Testing the accuracy of a four serum microRNA panel for the detection of primary bladder cancer: a discovery and validation study

Abstract

Background

Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC.

Methods

In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively.

Results

Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 − 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05).

Conclusion

The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.

CLINICAL SIGNIFICANCE

• Early detection and timely intervention can lead to a better prognosis of bladder cancer.

• This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer.

Keywords:

• Bladder cancer
• microRNA
• serum
• diagnosis

Authors’ contributions

C Lu contributed to the conduction of experiments and data processing. S Lin contributed to data arrangement and drafting of the manuscript. Z Wen, C Sun, Z Ge, W Chen, Y Li, P Zhang, Y Wu, W Wang, S Chen, H Zhou, X Li, H Li, L Tao, Y Hu, Z Zhao and Z Chen contributed to sample collection. Y Lai and X Wu contributed to reviewing/editing the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by Shenzhen High-level Hospital Construction Fund, Basic Research Project of Peking University Shenzhen Hospital (JCYJ2017001, JCYJ2017004, JCYJ2017005, JCYJ2017006, JCYJ2017007, JCYJ2017012), Clinical Research Project of Peking University Shenzhen Hospital (LCYJ2017001, LCYJ2020002, LCYJ2020020), Science and Technology Development Fund Project of Shenzhen (no. JCYJ20180507183102747) and Clinical Research Project of Shenzhen Health Commission (no. SZLY2018023).