記述言語：英語   出版者・発行元：Frontiers in Oncology  

Pancreatic cancer (PaC), which is characterized by a high mortality rate, is often diagnosed at an advanced stage, significantly limiting treatment effectiveness. Early detection is crucial for improving survival rates, especially for individuals at high risk (HR) for PaC. Traditional diagnostic methods, including ultrasound, computed tomography, and magnetic resonance imaging (MRI), have limited sensitivity, especially for detecting early-stage PaC. We explored the potential of miRNA from urinary extracellular vesicles (EVs) as a noninvasive diagnostic marker for PaC. An exploratory case–control study was conducted across multiple Japanese institutions. The study included 248 samples from patients with pancreatic ductal adenocarcinoma (PDAC), the most common type of PaC, and HR patients. Differential expression analysis revealed significant differences in 16 miRNAs between the PDAC and HR samples. A machine learning-based algorithm was developed based on these miRNAs to distinguish between PDAC and HR. The algorithm exhibited an AUC of 0.89, a sensitivity of 0.80, and a specificity of 0.79. The algorithm detected the early-stage PDAC (stage 0-IIA) with a sensitivity of 0.73. These findings highlight the potential of the urinary miRNA algorithm as a noninvasive tool to aid in the detection of PDAC, including early-stage cases, in high-risk populations.

DOI： 10.3389/fonc.2025.1682072

Open Access

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Npj Aging  

We aimed to develop and validate a urinary miRNA aging clock, positioning urine as a scalable, non-invasive aging-biomarker source. Using machine learning on 6331 adults, our clock achieved MAE ≈ 4.4 years (R² ≈ 0.79) in independent validation. The clock’s key biomarkers included well-established geromiRs miR-34a-5p, miR-31-5p, miR-146a-5p, and miR-155-5p. While slightly less accurate than DNA-methylation clocks, our model outperformed blood-based miRNA and mRNA clocks, underscoring urinary miRNAs as promising, truly non-invasive biomarkers of biological age and disease risk.

DOI： 10.1038/s41514-025-00311-3

Open Access

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：Scientific Reports  

Urinary extracellular vesicle (uEV)-derived microRNAs (miRNAs) have emerged as promising noninvasive biomarkers for disease prediction. However, fluctuations in urine concentration throughout the day may influence miRNA abundance and profiles, potentially limiting their clinical utility. To ensure the broader applicability of uEV-derived miRNAs in disease prediction, it is essential that their profiles remain stable regardless of collection time. In this study, we systematically examined factors influencing miRNA abundance in uEVs and assessed the stability of miRNA profiles. We collected serial urine samples from healthy individuals over three days and performed small RNA sequencing to analyze uEV-derived miRNA profiles in relation to various urine concentration parameters. Total miRNA counts were negatively correlated with urine volume and positively correlated with urine concentration indicators, including specific gravity and creatinine levels. miRNA profiles remained stable across different times and days when samples with low miRNA counts were excluded. These findings indicate that urine dilution is a major cause of variation in miRNA abundance. Our results highlight the importance of collecting adequately concentrated samples and provide foundational insights for developing standardized urine collection protocols, thereby facilitating the use of urinary uEV-derived miRNAs as robust and reliable biomarkers for disease prediction.

DOI： 10.1038/s41598-025-16728-5

Open Access

Web of Science

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PubMed

記述言語：英語   出版者・発行元：Cancers  

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.

DOI： 10.3390/cancers17162640

Open Access

Web of Science

Scopus

PubMed

記述言語：日本語   出版者・発行元：一般社団法人 日本消化器がん検診学会  

<p><b>【背景(目的)】</b>尿中N1,N12-ジアセチルスペルミンは, 腫瘍などの細胞から排出されるバイオマーカーとして注目されており, 尿を用いたがんの非侵襲的スクリーニングが期待されている。本研究では, がん患者と健康成人の尿サンプルを解析し, DiAcSpm/Cre値の診断性能の初期的な評価を行うことを目的とした。</p><p><b>【対象と方法】</b>2015年から2023年にかけて収集およびバイオバンクから取得した健康成人の尿サンプル78検体と, バイオバンクから取得したがん患者の尿サンプル125検体を解析した。尿中DiAcSpmを測定し, ROC曲線を用いて診断性能を評価した。</p><p><b>【結果】</b>尿中DiAcSpm/Cre値はがん患者群で有意に高く, 全体のROC曲線のAUCは0.82であった。特に大腸がんと胃がんでは早期ステージから高い診断性能が確認され, 膵臓がんではステージ進行に伴い性能が向上する傾向が見られた。</p><p><b>【結語】</b>尿中DiAcSpm/Cre値は大腸がんや胃がんの早期診断に有望であり, 膵臓がんでも進行に応じた有効性が示唆された。しかし, 尿検体の保管期間や国籍差が結果に影響する可能性があるため, 今後の研究でその影響を明らかにする必要がある。</p>

DOI： 10.11404/jsgcs.63.83

Open Access

CiNii Research