Table 2 The non-blood Liquid biopsy analytes and potential utility as diagnostic biomarkers
From: Liquid-based biomarkers in breast cancer: looking beyond the blood
No | Patient | Origin | Technology used | Method of detection | Readout | Function | Refs. |
|---|---|---|---|---|---|---|---|
1 | 49 patients with suspected BCLM | CSF | CellSearch | CTC | The detection of ≥ 1 CSF CTC was associated with a clinical sensitivity of 100% and a specificity of 77.3% for LM diagnosis | Predictina risk of leptomeningeal metastasis | [105] |
2 | 300 patients with 300 EBC and 50 healthy controls | Urine | ddPCR | ctDNA | A higher urinary ctDNA in BC patients. 38% of patients with EBC were detected with mutations who was found to have greater risk of recurrence | Early diagnostic biomarker/Predictina risk of relapse | [112] |
3 | 15 presurgical TNBC | Plasma/urine | Targeted sequencing | cfDNA | A total of 431 shared genetic variants were observed in both body fluids (NF1, CHEK2, KMT2C, PTEN and etc.) | Noninvasive biomarker | [113] |
4 | 1455 patients with EBC and 200 healthy controls | Serum/plasma/urine | ELISA /LC–MS/MS | CTC/ctDNA/TEPs/miRNA/Metabolomics | / | Breast Cancer Biobanking (PBCB) study | [31] |
5 | 250 patients with early BC and 50 healthy controls | Plasma/urine | ddPCR | cfDNA | The cfDNA was observed in plasma and urine measurements, with a sensitivity of 97%, a specificity of 100% and overall concordance of 99% | Noninvasive biomarker | [114] |
6 | 200 BC patients receiving neoadjuvant chemotherapy | Plasma/urine | ddPCR | cfDNA | A strong correlation was affirmed from urinary and plasma DNA at baseline with the correlation coefficient. Patients were divided into two subgroups based on postoperative urine DNA concentration. At 9th months, the HR between the two groups was 1.51 | Measure the severity/predict disease relapse | [115] |
7 | 200 patients with BC and 50 healthy controls | Plasma/urine | ddPCR | ctDNA | Index measurements demonstrate over 90% concordance with biopsy. Patients with lower risk of relapse experienced greater declines in detected DNA levels | Predict disease relapse | [116] |
8 | 24 patients with BCLM | CSF | WGS/ddPCR | ctDNA/plasma | ctDNA was detected in all samples derived from patients with BCLM. The suppression of CSF ctDNA was found to be closely associated with better survival time during intrathecal therapy | Predictina risk of leptomeningeal metastasis/Predicts therapeutic response | [97] |
9 | A HER2-positive mBC patient with brain metastases | Plasma/CSF | WES/ddPCR | ctDNA | Post-treatment ctDNA analysis showed decreased markers level in plasma, consistent with extra-CNS disease control, while increased in the CSF, confirming poor treatment benefit in the CNS | Predicts therapeutic response | [122] |
10 | 24 untreated, primary BC patients and 24 healthy controls | Urine | RT-qPCR | BC-related miRNAs | higher miR-155 levels and lower levels of miR-21, miR-125b, miR-451 in BC patients urine | Noninvasive biomarker | [126] |
11 | 10 breast cancer patients and 10 controls | Saliva | RT-qPCR/WB | Transcriptomes and proteomes | 8 saliva-based mRNA (S100A8, CSTA, GRM1, TPT1, GRIKI, H6PD, IGF2BP1, and MDM437) were significantly different between BC and controls. Evaluate the biomarkers in a cohort of 30 breast cancer patients and 63 controls | Early diagnosis biomarker | [127] |
12 | 69 BC patients and 40 healthy controls | Urine | RT-qPCR | exosomal miRNAs | A panel of four urinary microRNA types (miR-424, miR-423, miR-660, and let7-i) as a biomarker tool discriminating BC patients from healthy controls | Early diagnosis biomarker | [134] |
13 | 22 patients with early BC and 26 healthy controls | Urine | RT-qPCR/WB | miR-21/ MMP-1/CD63 in exosomes | MiR-21 expression was significant lower than in the controls. MMP-1/CD63 expression was significantly higher than in controls | Early diagnosis biomarker | [135] |
14 | 16 patients with MPE and 8 patients with non-malignant effusions | Pleural fluid | RT-qPCR | EV-miRNA | miR-1246 was increased, miR-1246 and miR-150-5p were dysregulation in the MPE | Noninvasive biomarker | [138] |
15 | 91 BC patients and 60 controls | Salivary | Biochemical analyses | Biochemical index | Salivary CA125 and sFA levels was higher in patients with BC | diagnosis biomarker( CA125/sFas) | [144] |
16 | 14 patients with MBC | Pleural fluid | WB | Â | The results revealed microvessel formation in the pleura of MBC and the underlying activation of p-JNK/VEGFR2 signaling | p-JNK/VEGFR2 signaling | [145] |
17 | 8 BC cases following chemotherapy | Stool | NMR Spectroscopy | Metabolite | amino acids were found to be upregulated, while lactate and fumaric acids were decreased in patients after treatment | Effect of chemotherapy | [87] |