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Zhang et al. Cancer Drug Resist 2024;7:30 https://dx.doi.org/10.20517/cdr.2024.62 Page 5 of 13

Figure 3. CircRNAs and miRNAs in the exosomes of breast cancer patients. Some circRNAs and miRNAs can be detected in the serum
exosomes of breast cancer patients, and analysis of exosomes in serum can provide information about the disease status.

high-grade BCs revealed that 25 miRNAs were significantly upregulated while 18 miRNAs were
significantly downregulated in high-grade cases . Additionally, 107 miRNAs were identified as potential
[39]
biomarkers for stratifying different types, grades, and stages of IDC .
[40]
The continuous discovery in research also indicates that miRNA and circRNA expression influence
proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT) in BC. Compared to
healthy controls, the expression levels of miR-144-3p, miR-23a-3p, miR-148a-3p, miR-130a-5p, and miR-
152-3p were lower in BC patients, which was associated with clinical stage and lymph node metastasis .
[41]
Overexpression of circRHOT1 and circ_0076611 enhanced the proliferative ability of triple-negative breast
cancer (TNBC) cells and promoted the proliferation, invasion, metastasis, and EMT of BC [42-44] . In addition,
miRNA and circRNA combined with other diagnostic markers can improve the sensitivity of BC diagnosis.
MiR-1910-3p in serum exosomes may be used as an effective diagnostic marker for BC diagnosis, and when
[45]
combined with CA153, it can improve the sensitivity of BC diagnosis . A combination of two miRNAs,
miR-4710 and miR-629-3p, along with three clinicopathologic factors, lymphovascular invasion, ultrasound
findings, and T stage, showed an AUC of 0.86, which may help diagnose ALN metastasis prior to surgery in
[46]
a less-invasive manner than SLNB .
However, there is still controversy about the application of miRNA in diagnosis. Several studies have found
that serum miR-21 expression is abnormally elevated in BC. By comparing miR-21 expression levels in the
plasma of 252 BC patients, 82 benign breast tumors, and 127 healthy controls, plasma miR-21 levels were
found elevated in BC patients, which were significantly decreased after surgery compared with
pre-operation. The results indicate that plasma miR-21 level is a crucial biomarker for BC diagnosis .
[47]
Additionally, the level of miR-21 in serum exosomes of BC patients with bone metastasis is significantly
elevated compared to other subgroups, reflecting the significance of miR-21 as a potential target for clinical
[48]
diagnosis of BC bone metastasis . In contrast, a publication reported that whole blood miR-21
concentration did not differ among pre-adjuvant therapy, post-adjuvant therapy patients, and healthy
individuals . In addition, plasma miR-21 concentration did not directly reflect tumor expression . These
[49]
[49]
findings reveal the lack of consistency and reproducibility in current studies of miRNA as biomarkers. The
reasons for these differences may be related to the differences in miRNA expression in different sample