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

Chong Lu; Shengjie Lin; Zhenyu Wen; Chen Sun; Zhenjian Ge; Wenkang Chen; Yingqi Li; Pengwu Zhang; Yutong Wu; Wuping Wang; Siwei Chen; Huimei Zhou; Xutai Li; Hang Li; Lingzhi Tao; Yimin Hu; Zhengping Zhao; Zebo Chen; Xionghui Wu; Yongqing Lai

doi:10.1080/1354750X.2024.2358312

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

Biomarkers. 2024 May 30:1-9. doi: 10.1080/1354750X.2024.2358312. Online ahead of print.

Authors

Chong Lu^{1

2}, Shengjie Lin^{1

3}, Zhenyu Wen^{1

3}, Chen Sun^{1

2}, Zhenjian Ge^{1

3}, Wenkang Chen^{1

3}, Yingqi Li^{1

4}, Pengwu Zhang^{1

5}, Yutong Wu^{1

3}, Wuping Wang^{1

4}, Siwei Chen^{1

4}, Huimei Zhou^{1

2}, Xutai Li^{1

2}, Hang Li¹, Lingzhi Tao¹, Yimin Hu¹, Zhengping Zhao¹, Zebo Chen¹, Xionghui Wu¹, Yongqing Lai¹

Affiliations

¹ Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, P.R. China.
² The fifth Clinical Medical College of Anhui Medical University, Hefei, Anhui, China.
³ Shantou University Medical College, Shantou, Guangdong, China.
⁴ Shenzhen University Health Science Center, Shenzhen, China.
⁵ Peking University Health Science Center, Beijing, China.

PMID: 38767408
DOI: 10.1080/1354750X.2024.2358312

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.

Keywords: Bladder cancer; diagnosis; microRNA; serum.

Plain language summary

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.