Circulating Tumour Cell Expression of Immune Markers as Prognostic and Therapeutic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Results
2.1. Included Studies and Patient Clinical Demographic Data
2.2. CTC Detection and Disease Stage
2.3. Immune Marker Expression and Disease Stage
2.4. HPV Status
2.5. CTC Immune-Marker Expression as Tumour Therapeutic and Treatment Response Biomarkers
2.6. Pre-Treatment (Baseline) CTC Immune Marker Expression as a Prognostic Biomarker
2.7. Post-Treatment CTC Immune Marker Expression
2.8. Study Quality
3. Discussion
4. Methods
4.1. Search Strategy and Inclusion Criteria
4.2. Study Selection and Data Extraction
4.3. Data Analysis
5. Conclusions
Supplementary Materials
Funding
Acknowledgments
Conflicts of Interest
References
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Author | Year | Tumour Site/Stage | No. of Patients in Cohort | Cohort Gender | Age (Years) | Tumour Site | CTC Enrichment Technique | Marker Detection Methodology | Immune Marker(s) | Timepoint of CTC Analysis | Outcome Measure (Median) and (Range) F/U |
---|---|---|---|---|---|---|---|---|---|---|---|
Strati et al. [18] | 2017 | Locally advanced HNSCC | 113 (pre-treatment = 94, post-treatment = 54) | Pre-treatment: M = 75, F = 19, post-treatment: M = 37, F = 17 | Pre-treatment: ≥65 = 40, <65 = 54, post-treatment: ≥65 = 25, <65 = 29 | Pre-treatment: Oropharynx = 21, Other = 73, Post-treatment: Oropharynx = 13, Other = 41 | Negative depletion (red cell lysis and CD45 MACS depletion) and EpCAM MACS enrichment | Gene expression using RT-qPCR | PD-L1 | Pre-treatment and post-treatment | PFS and OS [18.9 months (0.2–54.9)] |
Kulasinghe et al. [19] | 2018 | HNSCC stage I–IV | 23 | M = 17, F = 6 | <60 = 10, >60 = 23 | Oral cavity = 9, Oropharynx = 14 | Microfluidic (ClearCell FX CTChip marker-independent) enrichment | Surface marker assessment with IF antibody | PD-L1 | Pre-treatment | PFS [not stated] |
Chikamatsu et al. [20] | 2019 | R/M HNSCC | 30 | M = 27, F = 3 | Median 70.5 (range 53–86) | Oral cavity = 3, Nasopharynx = 1, Oropharynx = 3, Hypopharynx = 12, Larynx = 4, Paranasal sinuses = 6, Parotid gland = 1 | Negative depletion (density centrifugation and CD45 MACS depletion) | Gene expression using RT-qPCR | PD-L1, PD-L2, CD47 | R/M post-treatment | Biomarker of therapeutic PD-L1 target on tumour |
Tada et al. [21] | 2020 | HNSCC stage I–IV | 44 | M = 41, F = 3 | <66 = 21, ≥66 = 23 | Nasal cavity = 3, Oral cavity = 4, Nasopharynx = 2, Oropharynx = 17, Hypopharynx = 14, Larynx = 4 | CellSieve microfilter | Gene expression using RT-qPCR | PD-L1, PD-L2, CD47 | Pre-treatment | PFS and OS [not stated] |
Economopoulou et al. [22] | 2020 | Locally advanced HNSCC | 113 (pre-treatment = 94, post-treatment = 54) | Pre-treatment: M = 75, F = 19, post-treatment: M = 37, F = 17 | Pre-treatment: ≥65 = 40, <65 = 54, post-treatment: ≥65 = 25, <65 = 29 | Pre-treatment: Oropharynx = 21, Other = 73, post-treatment: Oropharynx = 13, Other = 41 | Negative depletion (red cell lysis and CD45 MACS depletion) and EpCAM MACS enrichment | Gene expression using RT-qPCR | IDO1 | Pre-treatment and post-treatment | PFS and OS [27.16 months (2.3–69.3)] |
Marker | PFS | OS | |||||
---|---|---|---|---|---|---|---|
Pre-Treatment | HR | 95% CI | p Value | HR | 95% CI | p Value | |
PD-L1 | Strati et al. 2017 | 1.43 | 0.63–3.25 | 0.39 | 0.55 | 0.23–1.30 | 0.17 |
Kulasinghe et al. 2018 | 5.16 | 1.01–26.33 | 0.049 | ||||
Tada et al. 2020 | 0.29 | 0.10–0.86 | 0.035 | not stated | not stated | 0.038 | |
PD-L2 | Tada et al. 2020 | 0.81 | 0.24–2.77 | 0.74 | 1.05 | 0.11–9.70 | 0.97 |
CD47 | Tada et al. 2020 | 1.56 | 0.51–4.69 | 0.45 | 2.21 | 0.33–12.97 | 0.45 |
IDO1 * | Economopoulou et al. 2020 | 0.23 | 0.02–0.50 | 0.018 | 0.57 | 0.19–1.36 | 0.21 |
Post-treatment | |||||||
IDO1 * | Economopoulou et al. 2020 | 1.20 | 0.25–3.23 | 0.75 | 2.92 | 1.11–7.70 | 0.011 |
PD-L1 * | Strati et al. 2017 | 4.07 | 1.67–9.91 | 0.002 ** | 7.96 | 2.65–23.89 | 0.0002 ** |
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Payne, K.; Pugh, M.; Brooks, J.; Batis, N.; Taylor, G.; Nankivell, P.; Mehanna, H. Circulating Tumour Cell Expression of Immune Markers as Prognostic and Therapeutic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2020, 21, 8229. https://doi.org/10.3390/ijms21218229
Payne K, Pugh M, Brooks J, Batis N, Taylor G, Nankivell P, Mehanna H. Circulating Tumour Cell Expression of Immune Markers as Prognostic and Therapeutic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences. 2020; 21(21):8229. https://doi.org/10.3390/ijms21218229
Chicago/Turabian StylePayne, Karl, Matthew Pugh, Jill Brooks, Nikolaos Batis, Graham Taylor, Paul Nankivell, and Hisham Mehanna. 2020. "Circulating Tumour Cell Expression of Immune Markers as Prognostic and Therapeutic Biomarkers in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis" International Journal of Molecular Sciences 21, no. 21: 8229. https://doi.org/10.3390/ijms21218229