MCAM/MUC18/CD146 as a Multifaceted Warning Marker of Melanoma Progression in Liquid Biopsy
Abstract
:1. Introduction
2. CD146 Molecular Expression as a Melanoma-Associated Marker in Peripheral Blood
3. CD146 as an Enrichment and Capture Marker for Circulating Melanoma Cells
4. Current Findings: CD146 as an Enrichment and Capture Marker at Melanoma Onset or Disease Recurrence
5. Current Findings: CD146 as an Enrichment and Capture Antigen and Molecular Expression Marker in Magnetically Immune CMC Fractions during Melanoma Follow-Up Time Course
6. Soluble CD146 Form in Melanoma Patients
7. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Sex | N° | % |
Female | 13 | 43.33 |
Male | 17 | 56.66 |
Age (Years) | 44 (mean) | 23–84 (range) |
Primary Tumour Site | N° | % |
Head and Neck * | 2 | 6.67 |
Trunk | 17 | 56.67 |
Extremity | 7 | 23.33 |
Unknown | 4 | 13.33 |
AJCC** Stage | N° | % |
>IB | 5 | 16.67 |
II: IIA (3); IIB (2); | 5 | 16.67 |
III ***: IIIA (2); IIIB (3); IIIC (2); | 7 | 23.33 |
IV | 13 | 43.33 |
Time from Diagnosis | Years | Pts/AJCC Stage |
Onset | 0–11 | 18: IB (5); IIA (3); IIB (2); IIIA (1); IIIB (1); IIIC (2); IV (4) |
First Observation–Baseline | 12: IIIA (1); IIIB (2); IV (9) | |
Clinical Status | % | |
Clinically Disease-Free | 12 | 40 |
Clinically Evident Disease | 18 | 60 |
Clinically Remission Expression Panel Patients Baseline Samples (#12) | CD146 5′-Portion | CD146 Long Isoform | CD146 Short Isoform | VE-Cadh | N-Cadh | VEGF | b-FGF | MMP-2 | MMP-9 |
---|---|---|---|---|---|---|---|---|---|
Endothelial CMCs (E-CMCs) (CD45-MCAM/CD16 +) | 16.6% 2/12 | 33.3% 4/12 | 33.3% 4/12 | 25% 3/12 | 33.3% 4/12 | 8.3% 1/12 | 33.3% 4/12 | 41.6% 5/12 | 41.6% 5/12 |
Stem-Mesenchimal CMCs (S-M-CMCs) (CD45-MCAM + ABCB5 +) | 8.3% 1/12 | 25% 3/12 | 16.6% 2/12 | 33.3% 4/12 | 25.0% 3/12 | 16.6% 2/12 | 16.6% 2/12 | 50.0% 6/12 | 33.3% 4/12 |
| |||||||||
Clinically Evident Disease Patients Expression Panel Baseline Samples (#18) | |||||||||
Endothelial CMCs (E-CMCs) (CD45-MCAM/CD16 +) | 44.4% 8/18 | 72.2% 13/18 | 61.1% 11/18 | 55.5% 10/18 | 33.3% 6/18 | 16.6% 3/18 | 11.1% 2/18 | 66.6% 12/18 | 55.5% 12/18 |
Stem-Mesenchimal CMCs (S-M-CMCs) (CD45-MCAM + ABCB5 +) | 50.0% 9/18 | 77.7% 14/18 | 72.2% 13/18 | 55.5% 10/18 | 27.7% 5/18 | 5.5% 1/18 | 22.2% 4/18 | 66.6% 12/18 | 72.2% 13/18 |
UPN | Sex | Age at Baseline | Primary Tumor Site | Histology | Breslow Grade (mm) | AJCC Status at Baseline | Incurrence of Progression from Diagnosis | Therapy after Diagnosis or Lymphnodal/Cutaneous in Transit/Metastases Incurrence | Follow-Up and Clinical Status |
---|---|---|---|---|---|---|---|---|---|
UPN1- AV | f | 80 | Unknown | / | / | IV | +1 year | Checkpoint inhibitors (anti-PD1-PD1L) | At +2 years: disease progression Actually in therapy |
UPN2- MU | m | 47 | Trunk | SSM | 1.8 | IIIA | +5 years | Targeted therapy (anti-BRAF and anti-MEK) | At +4 years: disease progression Actually clinical remission |
UPN3- FM | m | 40 | Trunk | SSM | 1.25 | IIB | +3 years | Pretargeted therapy (anti-BRAF and anti-MEK) | At +1 year: stable disease Actually in therapy |
UPN4- VM | m | 60 | Trunk | NM | 4.5 | IIB | +1 year | Checkpoint inhibitors (anti-PD1-PD1L) | At +2 years: continuous clinical remission |
UPN5- CAD | f | 82 | Acral | NM | 2.4 | IV | +13 years | Checkpoint inhibitors(anti-PD1-PD1L) | At +1 year: disease progression and death |
UPN6- PN | m | 64 | Trunk | NM | 4.0 | IV | +1 year | Targeted therapy (anti-BRAF and anti-MEK) | At +1 year: disease progression and death |
UPN7- ZF | m | 42 | Head | NM | 2.2 | IB | / | Checkpoint inhibitors (anti-PD1-PD1L) | At +2 years: continuous clinical remission |
UPN8- GD | m | 35 | Acral | NM | 2.2 | IIA | +7 years | Targeted therapy (anti-BRAF and anti-MEK) | At +1 year: continuous clinical remission |
UPN9- RETL | f | 53 | Acral | ALM | / | IIIC | / | Targeted therapy (anti-BRAF and anti-MEK) | At +2 years: clinical remission Actually stopped therapy |
UPN10- PME | f | 75 | Nasal cavity | Mucous MM | / | IIB | / | Checkpoint inhibitors (anti-PD1-PD1L) | At +6 months: disease progression Actually in therapy |
UPN11- DMM | f | 34 | Trunk | NM | 1.5 | IIIA | +2 years | IFN | At +6 years: continuous clinical remission Actually stop-therapy |
UPN12- SD | f | 41 | Trunk | NM | 7 | IIB | +2 years | Checkpoint inhibitors (anti-PD1-PD1L) | At +4 years: disease progression Actually in therapy |
UPN13- BC | m | 86 | Trunk | Trunk | 5 | IIB | +4 years | Refusal of any therapy | At +1 year: stable disease |
(A) | |||||||||
* Clinically Remission Patients | CD146 5′-Portion | CD146 Long Isoform | CD146 Short Isoform | VEGF | bFGF | N-Cadh | VE-Cadh | MMP-2 | MMP-9 |
Baseline Expression Panel (#7) | |||||||||
Endothelial CMCs (E-CMCs) (CD45-MCAM +) | 42.8% 3/7 | 85.7% 6/7 | 100% 7/7 | 57.1% 4/7 | 28.6% 2/7 | 71.4% 5/7 | 85.7% 6/7 | 85.7% 6/7 | 71.4% 5/7 |
Stem-Mesenchimal CMCs (S-M-CMCs) (CD45-MCAM + ABCB5+) | 42.8% 3/7 | 85.7% 6/7 | 100% 7/7 | 28.6% 2/7 | 57.1% 4/7 | 57.1% 4/7 | 71.4% 5/7 | 85.7% 6/7 | 71.4% 5/7 |
Follow-Up Expression Panel (#7) | |||||||||
Endothelial CMCs (E-CMCs) (CD45-MCAM +) | 0% 0/7 | 0% 0/7 | 0% 0/7 | 14.3% 1/7 | 14.3% 1/7 | 42.8% 3/7 | 0% 0/7 | 28.6% 2/7 | 28.6% 2/7 |
Stem-Mesenchimal CMCs (S-M-CMCs) (CD45-MCAM + ABCB5+) | 0% 0/7 | 0% 0/7 | 14.3% 1/7 | 0% 0/7 | 14.3% 1/7 | 0% 0/7 | 0% 0/7 | 0% 0/7 | 0% 0/7 |
(B) | |||||||||
Baseline Expression Panel (#8) | |||||||||
Endothelial CMCs (E-CMCs) (CD45-MCAM+) | 37.5% 3/8 | 62.5% 5/8 | 50.0% 4/8 | 12.5% 1/8 | 25.0% 2/8 | 25.0% 2/8 | 50.0% 4/8 | 62.5% 5/8 | 50.0% 4/8 |
Stem-Mesenchimal CMCs (S-M-CMCs) (CD45-MCAM + ABCB5+) | 50.0% 4/8 | 75.00% 6/8 | 62.5% 5/8 | 25.0% 2/8 | 50.0% 4/8 | 37.5% 3/8 | 62.5% 5/8 | 62.5% 5/8 | 87.5% 7/8 |
Follow-Up Expression Panel (#8) | |||||||||
Endothelial CMCs (CD45-MCAM + E-CMCs) | 37.5% 3/8 | 62.5% 5/8 | 100% 8/8 | 25.0% 2/8 | 25.0% 2/8 | 50.0% 4/8 | 62.5% 5/8 | 62.5% 5/8 | 87.5% 7/8 |
Stem-Mesenchimal CMCs (S-M-CMCs) (CD45-MCAM + ABCB5+) | 50.0% 4/8 | 87.5% 7/8 | 62.5% 5/8 | 37.5% 3/8 | 12.5% 1/8 | 25.0% 2/8 | 62.5% 5/8 | 62.5% 5/8 | 100% 8/8 |
Comparison Between Clinical Serum Classes | sCD146 ng/mL Dosage Mean/Median Healthy People Concentration = 273 ± 70 ng/mL |
---|---|
(A) Melanoma Baseline (Onset/First Observation) Sera (#30) | 199.55/186.78 Linear regression 201.01/191.40 Hyperbolic curve |
Melanoma Follow Up Sera (#21) | 258,28/230.60 Linear regression 260.26/232.85 Hyperbolic curve |
(B) Clinically Remission Patient Sera (#13) | 212.651/197.48 Linear regression 215.72/203.255 Hyperbolic curve |
Clinically Evident Disease Patient Sera (#22) | 262.13/259.16 Linear regression 263.88/261.22 Hyperbolic curve |
(C) Treatment-Naïve Patient Sera (#12) | 217.58/218.68 Linear regression 198.5/206.35 Hyperbolic curve |
Treated-Patient Sera (#22) (Checkpoint Inhibitor Therapy–Targeted Therapy–Other Therapies) | 253.85/235.33 Linear regression 255.87/237.82 Hyperbolic curve |
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Rapanotti, M.C.; Cugini, E.; Nuccetelli, M.; Terrinoni, A.; Di Raimondo, C.; Lombardo, P.; Costanza, G.; Cosio, T.; Rossi, P.; Orlandi, A.; et al. MCAM/MUC18/CD146 as a Multifaceted Warning Marker of Melanoma Progression in Liquid Biopsy. Int. J. Mol. Sci. 2021, 22, 12416. https://doi.org/10.3390/ijms222212416
Rapanotti MC, Cugini E, Nuccetelli M, Terrinoni A, Di Raimondo C, Lombardo P, Costanza G, Cosio T, Rossi P, Orlandi A, et al. MCAM/MUC18/CD146 as a Multifaceted Warning Marker of Melanoma Progression in Liquid Biopsy. International Journal of Molecular Sciences. 2021; 22(22):12416. https://doi.org/10.3390/ijms222212416
Chicago/Turabian StyleRapanotti, Maria Cristina, Elisa Cugini, Marzia Nuccetelli, Alessandro Terrinoni, Cosimo Di Raimondo, Paolo Lombardo, Gaetana Costanza, Terenzio Cosio, Piero Rossi, Augusto Orlandi, and et al. 2021. "MCAM/MUC18/CD146 as a Multifaceted Warning Marker of Melanoma Progression in Liquid Biopsy" International Journal of Molecular Sciences 22, no. 22: 12416. https://doi.org/10.3390/ijms222212416