Table 6.
Liquid biopsy based on other biofluids: the use of a broad spectrum of molecules as potential cancer biomarkers.
| Biomarker | Cancer Type | Study Characteristics | Study Results | Reference |
|---|---|---|---|---|
| Ascites-based liquid biopsy | ||||
| Malignant ascites | Gastrointestinal cancer | Patients diagnosed with malignant ascites of gastrointestinal cancer (n = 27) | Large amount of CD4+ and CD8+ T cells: exhausted phenotype → significant clinical relevance as prognostic and therapeutic target. | [30] |
| Pleural effusion | ||||
| EGFR (pleural effusion, ascites, pericardial effusion and cerebrospinal fluid) | Lung adenocarcinoma patients | Lung adenocarcinoma patients (n = 20) | Higher detection rate sensitivity of tumor-specific EGFR mutations in biofluid-supernatant-free DNA in comparison with biofluid sediment tumor cells and plasma-free DNA samples. | [187] |
| Bronchoalveolar lavage | ||||
| EGFR (bronchoalveolar lavage fluid, EVs) | NSCLC | NSCLC patients (n = 137) | EGFR genotyping by bronchoalveolar lavage fluid obtained from tumor site: high accuracy of diagnosis. | [153] |
| TMPRSS4 methylation (bronchoalveolar lavage and plasma) | NSCLC | Bronchoalveolar lavage: lung cancer patients (n = 79) and healthy controls (n = 26). Plasma: lung cancer patients (n = 89) and healthy controls (n = 25). |
Monitoring of surgically resected NSCLC patients. TMPRSS4 methylation status differentiates NSCLC and tumor-free subjects. |
[188] |
| Peritoneal lavage | ||||
| EV-isolated miRNAs (peritoneal lavage, ascites) | CRC | CRC patients (n = 25) and control patients (n = 25) | Source of potential biomarkers for CRC diagnosis (miRNA-199b-5p, miRNA-150-5p, miRNA-29c-5p, miRNA-218-5p, miRNA-99a-3p, miRNA-383-5p, miRNA-199a-3p, miRNA-193a-5p, miRNA-10b-5p and miRNA-181c-5p). | [38] |
| EV-isolated miRNAs (peritoneal lavage, ascites) | Endometrial cancer | Endometrial cancer patients (n = 25) and control patients (n = 25) | Deregulated miRNAs in endometrial cancer (n = 114) miRNAs. miRNA-383-5p, miRNA-10b-5p, miRNA-34c-3p, miRNA-449b-5p, miRNA-34c-5p, miRNA-200b-3p, miRNA-2110, and miRNA-34b-3p highlighted as promising biomarkers. |
[190] |
| KRAS and PIK3CA mutational analysis (peritoneal lavage, blood) | Endometrial cancer | Endometrial cancer patients (n = 50) | Approved feasibility of mutational analysis. Further studies needed to determine its use in the identification of patients with worse prognosis. | [191] |
| Uterine/utero-tubular lavage | ||||
| PTEN mutations (uterine lavage fluid) | Endometrial cancer | 67-year-old asymptomatic female | Identification of two oncogenic PTEN mutations nearly one year before the occurrence of symptoms | [192] |
| Genomic profiling (uterine aspirate, blood) | Endometrial cancer | Endometrial cancer patients (n = 60) | Potential applicability of combined use of different liquid biopsy for personalized cancer management. | [10] |
| Microvesicle proteomic profiling (utero-tubal lavage) | Ovarian cancer | High-grade ovarian cancer patients (n = 49) and controls (n = 127) | 9-protein classifier with 70% sensitivity and 76.2% specificity (identified all stage I lesions). | [35] |
| Cervical and vaginal secretions | ||||
| CA-125 (cervical and vaginal secretions, serum) | Endometrial cancer | Patients with polyps, hyperplasia or endometrial cancer (n = 97) and healthy subjects (n = 51) | Increased CA-125 in patients with complex hyperplasia and endometrial cancer. | [193] |
| Tear fluid | ||||
| Proteomic pattern | Breast cancer | Primary invasive breast carcinoma patients (n = 25) and healthy controls (n = 25) | Identified diagnostic protein biomarker to differentiate cancer patients from controls. | [150,194] |
| Breast cancer patients (n = 50) and healthy controls (n = 50) | ||||
| Tear exosomes (miRNAs) | Breast cancer | Metastatic breast cancer patients (n = 5) and healthy controls (n = 8) | Higher quantity of exosome markers in tears than in serum. Highly expressed miRNA-21 and miRNA-200c in tear exosomes of metastatic breast cancer patients in comparison with controls. |
[195] |
| Breast milk | ||||
| Proteins | Breast cancer | Ten milk samples from eight females | Identification of protein for early detection and accurate assessment of breast cancer. | [151] |
| Breast ductal fluid | ||||
| miRNAs | Unilateral breast cancer | Unilateral breast cancer patients (n = 22) | Feasibility of analyzing miRNAs. Discrimination of tumor histological subtypes. Discrimination of cancer and normal breast samples. |
[154] |
| Seminal fluid | ||||
| ctDNA (seminal plasma) | Prostate cancer | Prostate cancer patients (n = 6) and healthy controls (n = 3) | Different concentrations and fragment size of seminal plasma ctDNA in prostate cancer patients, benign prostate hyperplasia and healthy controls. | [33,152] |
| Prostate cancer patients (n = 30), benign prostate hyperplasia patients (n = 33), and healthy controls (n = 21) | ||||
Abbreviations: CA-125, the cancer antigen 125; CRC, colorectal carcinoma; ctDNA, circulating cell-free tumor DNA; EVs, extracellular vesicles; NSCLC, non-small cell lung cancer.