AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients Cohort
2.2. Immunohistochemistry
2.3. Fluorescence In Situ Hybridization
2.4. In Vitro Studies
2.4.1. Cell Lines
2.4.2. Western Blot Analysis
2.4.3. Cell Proliferation Assays
2.4.4. Colony Forming Assays
2.5. MET and AXL Co-Expression
2.6. Statistical Analysis
3. Results
3.1. Clinical and Pathological Characteristics of Patients
3.2. AXL IHC and FISH Results
3.3. MET IHC and FISH Results
3.4. AXL and MET Correlation
3.5. In Vitro Studies
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | N. (%) |
---|---|
All cases | 72 |
Age, years | |
>73 y | 41 (57%) |
<73 y | 31(43%) |
Gender | |
male | 61 (84%) |
female | 11 (16%) |
Histotype | |
Epithelial | 55(76.3%) |
Sarcomatoid | 9(12.5%) |
Biphasic | 8(11.1%) |
Disease stage | |
I | 32(44.4%) |
II | 24(33.3%) |
III | 10(13.8%) |
IV | 6(8.3%) |
Asbesto exsposure | |
yes | 57(79.1%) |
no | 7(9.7%) |
NA | 8(11.1%) |
Characteristics
n. (%) | AXL IHC n. (%) | MET IHC n. (%) |
AXL-MET
Co-Expression n. (%) | FISH AXL n. (%) | FISH MET n. (%) | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
- | + | - | + | - | + | NA | A | NA | A | ||
All cases | 72 | 61 (84.7) | 11 (15.3) | 57 (79.2) | 15 (20.8) | 65 (90.3) | 7 (9.7) | 62 (86.1) | 10 (13.9) | 71 (98.6) | 1 (1.4) |
Age, years | |||||||||||
>73 y | 41 (57%) | 31 (50.8) | 10 (90.9) | 32 (56.1) | 9 (60.0) | 34 (52.3) | 7 (100) | 35 (56.5) | 6 (60.0) | 40 (56.3) | 1 (100) |
<73 y | 31 (43%) | 30 (49.2) | 1 (9.1) | 25 (43.9) | 6 (40.0) | 31 (47.7) | 0 (0) | 27 (43.5) | 4 (40.0) | 31 (43.7) | 0 (0) |
Gender | |||||||||||
male | 61 (84%) | 50 (82.0) | 11 (100) | 47 (82.4) | 14 (93.4) | 54 (83.0) | 7 (100) | 52 (83.9) | 9 (90.0) | 60 (84.5) | 1 (100) |
female | 11 (16%) | 11 (18.0) | 0 (0) | 10 (17.6) | 1 (6.6) | 11 (17.0) | 0 (0) | 10 (16.1) | 1 (10.0) | 11 (15.5) | 0 (0) |
Histotype | |||||||||||
Epithelial | 55 (76.3%) | 44 (72.1) | 11 (100) | 42 (73.7) | 13 (86.6) | 48 (73.9) | 7 (100) | 47 (75.8) | 8 (80.0) | 54 (76.0) | 1 (100) |
Sarcomatoid | 9 (12.5%) | 9 (14.8) | 0 (0) | 9 (15.8) | 0 (0) | 9 (13.8) | 0 (0) | 9 (14.5) | 0 (0) | 9 (12.7) | 0 (0) |
Biphasic | 8 (11.1%) | 8 (13.1) | 0 (0) | 6 (10.5) | 2 (13.4) | 8 (12.3) | 0 (0) | 6 (9.7) | 2 (20.0) | 8 (11.3) | 0 (0) |
Disease stage | |||||||||||
I | 32 (44.4%) | 23 (37.7) | 9 (81.8) | 22 (38.6) | 10 (66.6) | 26 (40.0) | 6 (85.7) | 23 (37.1) | 9 (90.0) | 31 (43.7) | 1 (100) |
II | 24 (33.3%) | 23 (37.7) | 1 (9.1) | 21 (36.9) | 3 (20.0) | 23 (35.4) | 1 (14.3) | 23 (37.1) | 1 (10.0) | 24 (33.8) | 0 (0) |
III | 10 (13.8%) | 9 (14.8) | 1 (9.1) | 8 (14) | 2 (13.4) | 10 (15.4) | 0 (0) | 10 (16.1) | 0 (0) | 10 (14.0) | 0 (0) |
IV | 6 (8.3%) | 6 (9.8) | 0 (0) | 6 (10.5) | 0 (0) | 6 (9.2) | 0 (0) | 6 (9.7) | 0 (0) | 6 (8.5) | 0 (0) |
Asbesto exsposure | |||||||||||
yes | 57 (79.1%) | 48 (78.7) | 9 (81,8) | 46 (80.7) | 11 (73.4) | 51 (78.6) | 6 (85.7) | 49 (79.0) | 8 (80.0) | 57 (80.4) | 0 (0) |
no | 7 (9.7%) | 7 (11.5) | 0 (0) | 6 (10.5) | 1 (6.6) | 7 (10.7) | 0 (0) | 7 (11.3) | 0 (0) | 7 (9.8) | 0 (0) |
NA | 8 (11.1%) | 6 (9.8) | 2 (18.2) | 5 (8.8) | 3 (20.0) | 7 (10.7) | 1 (14.3) | 6 (9.7) | 2 (20.0) | 7 (9.8) | 1 (100) |
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Zito Marino, F.; Della Corte, C.M.; Ciaramella, V.; Erra, S.; Ronchi, A.; Fiorelli, A.; Vicidomini, G.; Santini, M.; Scognamiglio, G.; Morgillo, F.; et al. AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma. J. Pers. Med. 2022, 12, 1993. https://doi.org/10.3390/jpm12121993
Zito Marino F, Della Corte CM, Ciaramella V, Erra S, Ronchi A, Fiorelli A, Vicidomini G, Santini M, Scognamiglio G, Morgillo F, et al. AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma. Journal of Personalized Medicine. 2022; 12(12):1993. https://doi.org/10.3390/jpm12121993
Chicago/Turabian StyleZito Marino, Federica, Carminia Maria Della Corte, Vincenza Ciaramella, Stefania Erra, Andrea Ronchi, Alfonso Fiorelli, Giovanni Vicidomini, Mario Santini, Giosuè Scognamiglio, Floriana Morgillo, and et al. 2022. "AXL and MET Tyrosine Kinase Receptors Co-Expression as a Potential Therapeutic Target in Malignant Pleural Mesothelioma" Journal of Personalized Medicine 12, no. 12: 1993. https://doi.org/10.3390/jpm12121993