Table 1.
Summary of recent findings of MSI in cfDNA, ctDNA and CTCs from CRC.
| Source | Type | Year | Finding | Citation |
|---|---|---|---|---|
| cfDNA | 2 patients with MMR-D CRC tumors | 2017 | Effectiveness of the TMB report from cfDNA to predict MMR-D or MSI status and the possible response towards immunotherapy among CRC patients. | [105] |
| cfDNA | 13 CRC patients | 2018 | Feasibility of MSI detection in cfDNA with possible reflective of TMB in CRC. MSI assessment from cfDNA could predict clinical outcomes of immunotherapy. | [106] |
| cfDNA | Plasma from 29 metastatic cancers (19 CRC, 3 ampullary, 3 small intestine, 2 endometrial, 1 gastric, and 1 thyroid cancer) | 2019 | Development of a hybrid-capture-based 98 kb pan-cancer gene panel with a multifactorial error correction method and a novel peak-finding algorithm, capable of predicting progression-free survival in MSI and TMB-High patients treated with PD-1 blockade. | [107] |
| cfDNA | 1145 archived samples (residual plasma and/or cfDNA) collected and processed as part of routine standard-of-care clinical testing in the Guardant Health CLIA laboratory | 2019 | MSI assessment from cfDNA showed higher specificity, accuracy and sensitivity, with a detection limit of 0.1 percent of the tumor content than conventional tissue biopsy-based MSI detection. | [60] |
| cfDNA | Blood samples from 12 patients with MSI-H gastrointestinal tract cancer | 2019 | Detection of MSI status from cfDNA was possible via the Guardant Health Omni 2.0 mb panel. MSI-H cancer patients resistant to immune checkpoint blockade showed RNF43, APC and/or CTNNB1 mutations, suggesting the importance of co-activation of the WNT/B-Catenin pathway. | [109] |
| cfDNA | 30 plasma or serum from 14 patients with locally advanced CRC, mCRC or endometrial tumors | 2020 | The MSI-ddPCR assays were clinically sensitive, highly accurate and appropriate for the quantitative ctDNA detection in observational studies. | [89] |
| cfDNA | cfDNA sequencing data from 39 patients and 1565 WES samples from TCGA were treated as the training set | 2021 | Development of MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detect MSI status using cfDNA sequencing data with 100% accuracy within the LOD of 0.05% ctDNA content. | [124] |
| ctDNA | Plasma, matched tumor tissue and blood samples from 200 patients | 2018 | Correct identification of 13 MSI-H patients by MSI testing in ctDNA, in concordance with the results of MSI testing in tumor tissue with a sensitivity of 100%. | [61] |
| ctDNA | Plasma isolated from the peripheral blood from 222 consecutiveEGFR, KRAS, BRAF, and/or ESR1-positive NSCLC, colorectalcancer, or breast cancer patients | 2019 | Cell-free circulating tumor DNA-based MSI detection using Guardant360 was highly concordant with tissue-based testing, enabling highly accurate detection of MSI status concurrent with comprehensive genomic profiling. | [86] |
| CTCs | 8 single CTC from 8 individual CRC patients with matched tumor tissue | 2014 | Identification of disparity in MSI status between primary tumor, liver metastasis and individual isolated CTC. | [121] |
| CTCs | CTCs from peripheral blood of 198 mCRC patients | 2019 | Detection of CEACAM5 mRNA-positive CTCs as an adverse prognostic factor which correlated with poor clinical outcomes in MSI-high tumors patients. | [123] |
cfDNA = cell-free DNA, CRC = colorectal cancer, ctDNA = circulating tumor DNA, CTC = circulating tumor cell, ddPCR = droplet digital polymerase chain reaction, LOD = limit of detection, MMR-D = mismatch repair deficiency, mCRC = metastatic CRC, MSI = microsatellite instability, NSCLC = non-small cell lung cancer, TMB = tumor mutation burden, WES = whole exome sequencing.