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. 2025 Aug 13;17(16):2640.
doi: 10.3390/cancers17162640.

Urinary microRNAs as Prognostic Biomarkers for Predicting the Efficacy of Immune Checkpoint Inhibitors in Patients with Urothelial Carcinoma

Yosuke Hirasawa  1 , Atsushi Satomura  2   3 , Mitsuo Okada  1 , Mieko Utsugi  4 , Hiroki Ogura  1 , Tsuyoshi Yanagi  1 , Yuta Nakamori  1 , Masayuki Takehara  1 , Kokichi Murakami  1 , Go Nagao  1 , Takeshi Kashima  1 , Naoya Satake  1 , Yoriko Ando  2 , Motoki Mikami  2   3 , Mika Mizunuma  2 , Yuki Ichikawa  2   3 , Yoshio Ohno  1
Affiliations

Urinary microRNAs as Prognostic Biomarkers for Predicting the Efficacy of Immune Checkpoint Inhibitors in Patients with Urothelial Carcinoma

Yosuke Hirasawa et al. Cancers (Basel). .

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of urothelial carcinoma (UC); however, their efficacy varies among patients. Identifying reliable biomarkers to predict response to ICIs remains challenging. We aimed to explore urinary microRNAs (miRNAs) as potential biomarkers for predicting ICI efficacy in patients with UC. Methods: We prospectively collected urinary samples from patients with UC before ICI initiation and investigated the predictive value of urinary miRNAs in patients with UC receiving ICIs. The expression levels of these miRNAs in pretreated urine samples were analyzed using next-generation sequencing. The patients were categorized as responders (those with stable disease or better for >6 months) or nonresponders (those who experienced disease progression within 6 months of treatment initiation). Urinary miRNA levels were compared between the groups to assess their potential as predictive biomarkers. Results: Elevated expression of miR-185-5p and miR-425-5p in the responder group was significantly associated with improved overall and progression-free survival in patients with bladder cancer treated with ICIs (p < 0.05). Conversely, higher levels of miR-30a-5p and miR-542-3p in the nonresponder group were correlated with a poorer response to ICIs, suggesting a potential role in immune resistance. Conclusions: miR-185-5p and miR-425-5p can serve as predictive biomarkers of favorable ICI efficacy in bladder cancer, whereas miR-30a-5p and miR-542-3p could be associated with resistance mechanisms. These findings highlight the potential of miRNA-based biomarkers, particularly those found in urine samples, to guide personalized immunotherapeutic strategies for UC treatment.

Keywords: biomarker; bladder cancer; immune check point inhibitors; miRNA; urothelial carcinoma.

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Conflict of interest statement

M. Mizunuma and Y. Ichikawa are board members and shareholders of Craif Inc. A. Satomura, Y. Ando, and M. Mikami are employees of Craif Inc. and hold stock options in the company. The remaining 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
Study design.
Figure 2
Figure 2
Principal component analysis of microRNA (miRNA) profiles revealed a clear separation between responders (R) and nonresponders (NR) (a). Differential expression analysis identified six miRNAs upregulated in R and four miRNAs upregulated in NR (b,c).
Figure 3
Figure 3
Progression-free survival (PFS) stratified by urinary microRNA (miRNA) levels upregulated in responders (R). Kaplan–Meier curves of PFS in patients grouped into high and low expression by median levels of six urinary miRNAs identified as significantly upregulated in R.
Figure 4
Figure 4
Progression-free survival (PFS) stratified by urinary microRNA (miRNA) levels upregulated in non-responders (NR). Kaplan–Meier curves of PFS in patients grouped into high and low expression by median levels of six urinary miRNAs identified as significantly downregulated in responders (R).
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