Background <p>Muscle-invasive urothelial carcinoma (MIUC) poses higher risks of recurrence and metastasis compared with non-muscle-invasive urothelial carcinoma (NMIUC). However, difficulties in early detection and the invasive nature of current diagnostic procedures. Using next-generation sequencing (NGS), we aimed to profile comprehensive surveillance of urinary microRNAs (miRNAs) as a promising non-invasive tool for assessing urothelial carcinoma (UC) and identify differentially expressed miRNAs (DEmiRNAs) in patients with MIUC or NMIUC, providing insights into UC progression and molecular mechanisms in Taiwanese patients. We analyzed the clinical differences between patients with MIUC or NMIUC in treatment-naïve patients.</p> Methods <p>Urinary miRNAs were profiled using NGS. DEmiRNAs were identified with DESeq2, and target prediction was performed using TarBase-v9.0 and DIANA-microT. Enrichment analysis was conducted with the miEAA tool to link DEmiRNAs to biological pathways and processes, focusing on the KEGG pathways and Gene Ontology (GO) annotations.</p> Results <p>Among the 52 participants, significantly more patients with MIUC used herbal medicines compared with the NMIUC group (<i>p</i> = 0.027). A total of 1,967 DEmiRNAs were detected comprehensively, with 691 upregulated and 232 downregulated in MIUC versus NMIUC. Notably, hsa-miR-3168 exhibited the highest upregulation (10.2-fold), while hsa-miR-511-3p was the most downregulated (9.32-fold). KEGG analysis revealed that upregulated DEmiRNAs were most enriched in amino acid biosynthesis pathways, while downregulated DEmiRNAs were associated with the Hedgehog signaling pathway.</p> Conclusions <p>This study highlights urinary DEmiRNAs detected via NGS as a potential non-invasive diagnostic tool. Pathway analyses of DEmiRNAs provided valuable insights into UC progression and offers opportunities for future therapeutic development.</p>

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Comprehensive surveillance of MicroRNA to discriminate between muscle-invasive and non-muscle-invasive urothelial carcinoma based on noninvasive urinary small RNA sequencing in Taiwanese patients

  • I-Ning Yang,
  • Chun-An Liang,
  • Chia-Chun Wu,
  • Qian-Sheng Xu,
  • Shang-Wen Lin,
  • Ming-Cheng Wang,
  • Ming-Jenn Chen,
  • Yuan-Shuo Hsueh,
  • Hui Hua Chang

摘要

Background

Muscle-invasive urothelial carcinoma (MIUC) poses higher risks of recurrence and metastasis compared with non-muscle-invasive urothelial carcinoma (NMIUC). However, difficulties in early detection and the invasive nature of current diagnostic procedures. Using next-generation sequencing (NGS), we aimed to profile comprehensive surveillance of urinary microRNAs (miRNAs) as a promising non-invasive tool for assessing urothelial carcinoma (UC) and identify differentially expressed miRNAs (DEmiRNAs) in patients with MIUC or NMIUC, providing insights into UC progression and molecular mechanisms in Taiwanese patients. We analyzed the clinical differences between patients with MIUC or NMIUC in treatment-naïve patients.

Methods

Urinary miRNAs were profiled using NGS. DEmiRNAs were identified with DESeq2, and target prediction was performed using TarBase-v9.0 and DIANA-microT. Enrichment analysis was conducted with the miEAA tool to link DEmiRNAs to biological pathways and processes, focusing on the KEGG pathways and Gene Ontology (GO) annotations.

Results

Among the 52 participants, significantly more patients with MIUC used herbal medicines compared with the NMIUC group (p = 0.027). A total of 1,967 DEmiRNAs were detected comprehensively, with 691 upregulated and 232 downregulated in MIUC versus NMIUC. Notably, hsa-miR-3168 exhibited the highest upregulation (10.2-fold), while hsa-miR-511-3p was the most downregulated (9.32-fold). KEGG analysis revealed that upregulated DEmiRNAs were most enriched in amino acid biosynthesis pathways, while downregulated DEmiRNAs were associated with the Hedgehog signaling pathway.

Conclusions

This study highlights urinary DEmiRNAs detected via NGS as a potential non-invasive diagnostic tool. Pathway analyses of DEmiRNAs provided valuable insights into UC progression and offers opportunities for future therapeutic development.