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. 2024 Dec 24:14:1470457.
doi: 10.3389/fonc.2024.1470457. eCollection 2024.

Panel containing three serum microRNAs: a promising biomarker for early detection of bladder cancer

Affiliations

Panel containing three serum microRNAs: a promising biomarker for early detection of bladder cancer

Zhenjian Ge et al. Front Oncol. .

Abstract

Background: Bladder cancer (BC) is a common tumor worldwide. Screening for BC currently lacks a highly efficient, non-invasive, and inexpensive method. Serum microRNA (miRNA), which is stable and commonly present, has the potential to serve as a novel marker for BC diagnosis.

Materials & methods: Based on a study involving 112 BC patients and 112 healthy subjects, we conducted this research in three phases to identify applicable microRNAs (miRNAs) in serum for BC diagnosis using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A panel with optimal diagnostic value was developed. Additionally, we used bioinformatic analysis to explore the potential biological functions of the crucial miRNAs.

Results: The diagnostic panel consisted of miR-212-3p, miR-30c-5p, and miR-206, with an area under the curve (AUC) of 0.838, sensitivity of 83.33%, and specificity of 73.81%. Furthermore, ATF3, GJA1, JPH2, MVB12B, RUNX1T1, SLC8A1, SPATA6, and TPM3 may be potential target genes of these three miRNAs.

Conclusion: We developed a three-miRNA panel that could serve as a highly efficient and inexpensive biomarker for BC diagnosis and screening.

Keywords: MiR-212-3p; biomarker; bladder cancer; miR-206; miR-30c-5p; microRNA.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of study design. BC, bladder cancer; HCs, healthy controls.
Figure 2
Figure 2
Relative serum expression of ten candidate miRNAs in training phase. Expression profiles of ten candidate miRNAs in serum samples from 28 BC patients and 28 HCs. Screening criteria: p-value < 0.05, *p < 0.05, ***p < 0.001. BC, bladder cancer; HCs, healthy controls.
Figure 3
Figure 3
Serum expression and ROC curve analysis of five miRNAs in validation stage. Downregulated expression levels of (A) miR-142-3p, (E) miR-200-5p, (G) miR-206, and (I) miR-212-3p in the serum of BC patients compared to HCs, and (C) upregulated expression level of miR-30c-5p in the serum of BC patients. ROC curve analyses of (B) miR-142-3p, (D) miR-30c-5p, (F) miR-200-5p, (H) miR-206, and (J) miR-212-3p. **p < 0.01, ***p < 0.001.
Figure 4
Figure 4
ROC curve analysis of three-miRNA panel (miR-212-3p, miR-30c-5p, and miR-206). The AUC of the panel is 0.838 (95% CI: 0.774–0.890; sensitivity = 83.33%, specificity = 73.81%).
Figure 5
Figure 5
Prediction of target genes by miRWalk 2.0 for three critical miRNAs. (A) Venn diagram illustrating genes targeted by two or more miRNAs (a total of 462 genes). The expression of 33 putative genes targeted by all three miRNAs in 404 BC patients and 28 healthy controls was verified through GEPIA. Eight genes have abnormal expression in BC (|log2FC| > 1.5, p < 0.01): ATF3 (B), GJA1 (C), JPH2 (D), MVB12B (E), RUNX1T1 (F), SLC8A1 (G), SPATA6 (H), TPM3 (I). *p<0.01.
Figure 6
Figure 6
GO functional annotation and KEGG pathway enrichment analysis of the target genes of miR-212-3p, miR-30c-5p, and miR-206. (A) Biological process analysis; (B) cellular component analysis; (C) molecular function analysis; (D) KEGG pathway enrichment analysis.

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