Abstract
Abstract BACKGROUND: MicroRNAs have emerged as new diagnostic and therapeutic biomarkers for breast cancer. Herein, we analyzed miR-99a-5p expression levels in primary tumours and plasma of breast cancer patients to evaluate its usefulness as a minimally invasive diagnostic biomarker. METHODS: MiR-99a-5p expression levels were determined by quantitative real-time PCR in three indepent cohorts of patients: I) Discovery cohort: breast cancer tissues (n=103) and healthy breast tissues (n=26). II) Testing cohort: plasma samples from 105 patients and 98 healthy donors. III) Validation cohort: plasma samples from 89 patients and 85 healthy donors. Receiver operating characteristic (ROC) curve analyses were applied to evaluate the diagnostic potential of miR-99a-5p expression levels in tissue and plasma samples. RESULTS: MiR-99a-5p was significantly downregulated in breast cancer tissues compared to healthy breast tissues (p < 0.0001), being able to discriminate BC from healthy breast tissues with an AUC of 0.85, 87.38% sensitivity, 76.92% specificity, and 85.27% accuracy. Conversely, miR-99a-5p levels were significantly higher in breast cancer patients than in healthy controls in plasma samples from both testing and validation cohorts (p < 0.0001). ROC curve analysis revealed that miR-99a-5p has good diagnostic potential, with an AUC of 0.76, 63.81% sensitivity, 79.59% specificity, and 71.43% accuracy. The value of circulating miR-99a-5p levels as a breast cancer biomarker was further validated in an independent cohort, where it was able to identify breast cancer with 57.30% sensitivity, 67.06% specificity, and 62.07% accuracy. Besides, we also confirmed that circulating miR-99a-5p levels were able to discriminate early breast cancer from healthy controls with a 66.67% accuracy, 68.80% sensitivity, 65.28% specificity, and an AUC of 0.69 (p < 0.0001). CONCLUSION: MiR-99a-5p’s deregulated expression distinguished healthy individuals from breast cancer patients in two different types of samples (tissues and plasma). Interestingly, plasma expression levels were significantly lower in healthy controls than in early-stage breast cancer patients. Our findings suggest that circulating miR-99a-5p as a novel promising non-invasive biomarker for breast cancer detection. Citation Format: Iris Garrido-Cano, Vera Constâncio, Anna Adam-Artigues, Ana Lameirinhas, Soraya Simón, Belen Ortega, María Teresa Martínez, Cristina Hernando, Begoña Bermejo, Ana Lluch, Paula Lopes, Rui Henrique, Carmen Jerónimo, Juan Miguel Cejalvo, Pilar Eroles. Circulating miR-99a-5p expression in plasma: A potential biomarker for early diagnosis of breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-31.
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