Abstract PO2-14-02: Clinical significance of urinary microRNA expression in primary breast cancer
Authors: Inoue Yuka , Uehiro Natsue , Yamashita Nami , Yamaguchi Hiroki , Maezono Sakura , Palfalvi Mariko , Ando Yoriko , Nishiyama Yumi , Mizunuma Mika , Ichikawa Yuki , Matsunaga Yuki , Iesato Asumi , Ozaki Yukinori , Maeda Tetsuyo , Takahashi Yoko , Hara Fumitaka , Kobayashi Takayuki , Osako Tomo , Sakai Takehiko , Ueno Takayuki , Ohno Shinji 
Published: May 2024

Abstract
Backgrounds: MicroRNAs (miRNAs) are small functional nucleic acids that regulate homeostasis by maintaining a balance of regulatory functions within cells. In humans, more than 2,000 miRNAs have been discovered, and each type of cancer has its own unique pattern of miRNA expression. Like circulating tumor DNA, miRNAs circulate in the blood in the form of exosomes, and some of them are excreted in the urine. Therefore, miRNAs in blood and urine are considered potential biomarkers in cancer. We examined miRNAs in urine, which can be collected without invasive procedures. Aims: This study aimed to investigate the clinical significance of urinary microRNA in primary breast cancer. Patients: Two hundred patients with stage 0-III primary breast cancer treated in our hospital (breast cancer group) and 105 healthy volunteers (control group) were included in the study. Methods: Small RNA seq was performed using a next-generation sequencer, and urinary miRNA profiles were obtained and analyzed. Student’s t-tests were conducted between breast cancer group and the control group, and miRNAs with p-values p-values &lt; 0.05 and Log2FC&gt;0.5 were differentially expressed-miRNAs(DEMs). In the present study, miEAA API version2.0 and miRDIP were used to predict the target genes of the functional DEMs. The functional enrichment of the target genes of the DEMs was assessed using KEGG signalling pathway analyses. A machine learning model for binary classification of breast cancer and control group was created and its performance was evaluated using cross-validation method. Results: The median age was 50.3 years old in the breast cancer group and 46.1 years old in the control group. Of the breast cancer group, 13.5% were at clinical stage 0. Approximately 80% of the patients had HR+HER2- tumors. Twenty-eight miRNAs were identified to differentiate between the breast cancer group and the control group. Of the 28 miRNAs, fifteen miRNAs were up-regulated and thirteen miRNAs were down-regulated in the breast cancer group and compared to the control group. Pathway analysis revealed that miRNAs upregulated in the breast cancer group were associated with the PI3K-Akt signaling pathway and the MAPK signaling pathway. No association was observed between expression patterns of the identified miRNAs and clinicopathological factors other than nodal status and lymphatic invasion, including tumor size and hormone receptor/HER2 expressions. MicroRNA-486-5p, miRNA-486-3p and miRNA-126-3p expressions were decreased in patients with lymph node metastasis or lymphatic invasion. A machine learning model using urinary miRNAs identified breast cancer with an accuracy of AUC=0.83. The model maintained accuracy to diagnose breast cancer at any stage including ductal carcinoma in situ (DCIS), suggesting its usefulness in screening for early-stage cancers, including DCIS. Discussion: Previous reports have shown that miRNA-486-5p and miRNA-486-3p in breast cancer tissues are downregulated in patients with lymph node metastasis, and miRNA-126-3p is downregulated in patients with positive sentinel lymph nodes, which were consistent with the present study urine. This is the same trend as in the present study, which was conducted in using urine miRNAs. Conclusion: We identified miRNAs in urine to differentiate primary breast cancer from healthy controls. The miRNA-486 may correlate with lymph node metastasis and lymphatic invasion.
Citation Format: Yuka Inoue, Natsue Uehiro, Nami Yamashita, Hiroki Yamaguchi, Sakura Maezono, Mariko Palfalvi, Yoriko Ando, Yumi Nishiyama, Mika Mizunuma, Yuki Ichikawa, Yuki Matsunaga, Asumi Iesato, Yukinori Ozaki, Tetsuyo Maeda, Yoko Takahashi, Fumitaka Hara, Takayuki Kobayashi, Tomo Osako, Takehiko Sakai, Takayuki Ueno, Shinji Ohno. Clinical significance of urinary microRNA expression in primary breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-14-02.