Abstract
PurposeMicroRNAs can influence many biological processes and have shown promise as cancer biomarkers. Few studies have focused on the expression of microRNA-223 (miR-223) and its precise role in breast cancer (BC). We aimed to examine the expression level of miR-223 and its prognostic value in BC.MethodsTissue microarray (TMA)-based miRNA detection in situ hybridization (ISH) with a locked nucleic acid (LNA) probe was used to detect miR-223 expression in 450 BC tissue samples. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using the Kaplan-Meier method and Cox regression model.ResultsOS and DFS were prolonged in the high miR-223 expression group compared to the low miR-223 expression group (p < 0.0001 and p = 0.017, respectively), especially in patients with the triple-negative breast cancer (TNBC) subtype (p = 0.046 and p < 0.001, respectively). Univariate and multivariate Cox regression analyses revealed that TNM stage (p = 0.008), the molecular subtype (p = 0.049), and miR-223 (p < 0.001) were independently associated with OS and DFS. External validation was performed with the METABRIC and The Cancer Genome Atlas (TCGA) databases via online webtools and was consistent with the data described above.ConclusionsThis study provides evidence that high miR-223 expression at diagnosis is associated with improved DFS and OS for BC patients, especially those with the TNBC subtype. miR-223 is a valid and independent prognostic biomarker in BC.
Highlights
Breast cancer (BC) has overtook lung cancer as leading cause of cancer worldwide
The four molecular subtypes (Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative, definitions described in Table 1) accounted for 22, 24, 20.67, and 33.33%, respectively
In the detailed subtype analysis, we found that high miR-223 expression levels were associated with prolonged Overall survival (OS) in patients with triple-negative breast cancer (TNBC) but not in those with the other subtypes based on data from the METABRIC database (p = 0.0054; Figure 3C), consistent with the results described above
Summary
Breast cancer (BC) has overtook lung cancer as leading cause of cancer worldwide (https://www.iarc.who.int/wp-content/ uploads/2021/02/pr294_E.pdf). Since the groundbreaking work of Sørlie T and colleagues [2, 3] at the beginning of the 21st century, BC has been believed to consist of at least four different clinically relevant molecular subtypes, Luminal A, Luminal B, HER2 enriched, and triple-negative, classified according to the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Numerous new biomarkers are still being researched to help optimize personalized treatment in the management of BC, especially triple-negative breast cancer (TNBC), which has a high risk of recurrence and no effective targeted therapy [6, 7]
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