Breast cancer is the second cause of cancer-associated death among women and seriously endangers women’s health. Therefore, early identification of breast cancer would be beneficial to women’s health. At present, circular RNA (circRNA) not only exists in the extracellular vesicles (EVs) in plasma, but also presents distinct patterns under different physiological and pathological conditions. Therefore, we assume that circRNA could be used for early diagnosis of breast cancer.
Researchers at Southern Medical University have developed classifiers for breast cancer diagnosis that relied on 259 samples, including 144 breast cancer patients and 115 controls. In the discovery stage, they compared the genome-wide long RNA profiles of EVs in patients with breast cancer (n=14) and benign breast (n=6). To further verify its potential in early diagnosis of breast cancer, they prospectively collected plasma samples from 259 individuals before treatment, including 144 breast cancer patients and 115 controls. Finally, the researchers developed and verified the predictive classifies based on their circRNA expression profiles of plasma EVs by using multiple machine learning models. By comparing their circRNA profiles, the researchers found 439 circRNAs with significantly different levels between cancer patients and controls.
RNA composition in EVs
(A) The types of RNAs in EVs. (B) Annotation of circRNAs. (C) Source of circRNAs. (D) Length distribution of circRNAs. nt, Nucleotide. All, all of individuals. Overlap, sense overlapping circRNAs.
Considering the cost and practicability of the test, they selected 20 candidate circRNAs with elevated levels and detected their levels by quantitative real-time polymerase chain reaction. In the training cohort, they found that BCExoC, a nine-circRNA combined classifier with SVM model, achieved the largest AUC of 0.83 [95% CI 0.77-0.88]. In the validation cohort, the predictive efficacy of the classifier achieved 0.80 [0.71-0.89]. This work reveals the application prospect of circRNAs in plasma EVs as non-invasive liquid biopsies in the diagnosis and management of breast cancer.