Abstract 2604: Urinary microRNAs as biomarkers for early detection of urothelial cancer

Kazuya Takayama, Kohei Yamazaki, H. Yamaguchi, Keishu Tsuda, T. Yasui, Y. Ichikawa
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Abstract

microRNAs modulate gene expression in various cancer types, and their profiles differ in healthy and cancer groups of people and they represent a warning sign for various cancer scenarios. Identification of tumor-specific microRNAs presents a powerful opportunity to potentially reduce cancer mortality through early detection. In order to achieve early detection through population screening, noninvasive approaches are needed to complement and improve upon current strategies for urothelial cancer (UC) screening. Since all microRNAs in the blood cannot be transferred from donor to recipient cells during single blood circulation, kidney filtration could pass some untransferred microRNAs from blood to urine, therefore urinary microRNAs might be used as biomarkers for the diagnosis of cancer. We investigated whether urine levels of microRNA can differentiate patients with UC from healthy individuals. Here, we successfully identified UC-related microRNA ensembles in urine through a combination of microfluidic microRNA extraction device and machine learning-based analysis. We analyzed 93 urine samples from 27 UC patients and 66 healthy individuals (controls). An initial set of 74 microRNAs was selected by microarray microRNA profiling assay as biomarker candidates. Quantitative reverse-transcription PCR was used for further analysis to validate the expression of microRNAs. We selected a group of 6 microRNAs for validation; (miR-6089, miR-4488, miR-4784, miR-26a-5p, miR-148a-3p, and miR-143-3p) were confirmed to be significantly different in UC and controls. We adopted a logistic regression model and successfully developed a classifier based on these 6 microRNAs, which showed remarkably high sensitivity (94%) and specificity (85%). In summary, patients with UC have significantly different patterns of microRNA expression from healthy individuals. We identified a signature of 6 microRNAs as predictors that can differentiate patients with UC from those who are healthy. These microRNAs could be potentially developed as biomarkers for UC. Citation Format: Kazuya Takayama, Kohei Yamazaki, Hiroki Yamaguchi, Keishu Tsuda, Takao Yasui, Yuki Ichikawa. Urinary microRNAs as biomarkers for early detection of urothelial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2604.
摘要2604:尿微rna作为尿路上皮癌早期检测的生物标志物
microrna调节各种癌症类型的基因表达,它们的特征在健康人群和癌症人群中有所不同,它们代表了各种癌症情景的警告信号。肿瘤特异性microrna的鉴定为通过早期检测潜在地降低癌症死亡率提供了一个强大的机会。为了通过人群筛查实现早期发现,需要非侵入性方法来补充和改进当前的尿路上皮癌(UC)筛查策略。由于血液中的所有microrna不能在单次血液循环中从供体细胞转移到受体细胞,肾脏过滤可以将一些未转移的microrna从血液传递到尿液,因此尿液中的microrna可能用作癌症诊断的生物标志物。我们研究了尿中microRNA水平是否可以区分UC患者和健康人。在这里,我们通过微流控microRNA提取装置和基于机器学习的分析相结合,成功地鉴定了尿中uc相关的microRNA集合。我们分析了来自27名UC患者和66名健康个体(对照组)的93份尿液样本。通过微阵列分析筛选出74个microRNA作为候选生物标志物。采用定量反转录PCR进一步分析验证microrna的表达。我们选择了一组6个microrna进行验证;(miR-6089, miR-4488, miR-4784, miR-26a-5p, miR-148a-3p和miR-143-3p)在UC和对照组中被证实存在显著差异。我们采用逻辑回归模型,成功开发了基于这6个microrna的分类器,该分类器具有非常高的灵敏度(94%)和特异性(85%)。总之,UC患者的microRNA表达模式与健康个体明显不同。我们确定了6个microrna作为区分UC患者和健康患者的预测因子。这些microrna可能被开发为UC的生物标志物。引文格式:Kazuya Takayama, Kohei Yamazaki, Hiroki Yamaguchi, Keishu Tsuda, Takao Yasui, Yuki Ichikawa。尿微rna作为尿路上皮癌早期检测的生物标志物[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):2604。
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