Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma
Abstract
:1. Introduction
2. Results
2.1. Patient Demographics and Tumor Information
2.2. Integrin α5 Protein Expression
2.3. Treatment
2.4. Survival
3. Discussion
4. Materials and Methods
4.1. Patients and Tissue Samples
4.2. Patient-Derived Xenografts
4.3. Immunohistofluorescence
4.4. Western Blot
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinicopathological Features | Total No. of Patients | With | With | |
---|---|---|---|---|
Low α5 | High α5 | p-Value * | ||
Expression | Expression | |||
n | 95 | 47 | 48 | |
Age, n (%) | ||||
≥60 | 36 (38) | 19 (40) | 17 (35) | 0.6752 |
<60 | 59 (62) | 28 (60) | 31 (65) | |
Gender, n (%) | ||||
Male | 61 (64) | 26 (55) | 35 (73) | 0.0891 |
Female | 34 (36) | 21 (45) | 13 (27) | |
Resection degree, n (%) | ||||
Biopsy | 20 (21) | 6 (13) | 14 (29) | |
Partial resection | 34 (36) | 18 (38) | 16 (33) | 0.1410 |
Macroscopic resection | 41 (43) | 23 (49) | 18 (38) | |
RPA score, n (%) | ||||
<V | 37 (39) | 17 (36) | 20 (42) | |
≥V | 37 (39) | 19 (40,5) | 18 (37) | 0.8575 |
Unknown | 21 (22) | 11 (23,5) | 10 (21) | |
MGMT promoter status, n (%) | ||||
Methylated | 31 (33) | 17 (36) | 14 (29) | |
Un-methylated | 28 (29) | 14 (30) | 14 (29) | 0.6962 |
Unknown | 36 (38) | 16 (34) | 20 (42) | |
P53 gene status, n (%) | ||||
Mutated (antigen detected in >10% cells) | 13 (14) | 3 (6) | 10 (21) | |
Wild-type (<10% cells) | 5 (5) | 2 (4) | 3 (6) | 0.0912 |
Unknown | 77 (81) | 42 (90) | 35 (73) | |
Stupp protocol, n (%) | ||||
Completed | 58 (61) | 28 (60) | 30 (63) | |
Un-completed | 24 (25,5) | 12 (25) | 13 (27) | 0.4670 |
None | 4 (4) | 1 (2) | 2 (4) | |
Unknown | 9 (9,5) | 6 (13) | 3 (6) | |
Recurrence treatment, n (%) | ||||
None | 35 (37) | 14 (30) | 21 (44) | |
Second-line treatment | 40 (42) | 19 (42) | 20 (42) | |
-Chemotherapy | 30 (32) | 14 (30) | 16 (33) | 0.2103 |
-Bevacizumab | 23 (24) | 9 (19) | 14 (29) | |
Unknown or NA | 20 (21) | 14 (30) | 7 (15) | |
α5 expression level (A.U.) Mean ± SE | 320 ± 17 | 213 ± 4 | 425 ± 28 | p < 0.0001 |
Variables | PFS | OS | ||||||
---|---|---|---|---|---|---|---|---|
n | HR | 95% CI | p * | n | HR | 95% CI | p * | |
Age | ||||||||
≥60 years vs. <60 years | 76 | 1.827 | 1.040–3.210 | 0.0359 | 95 | 1.989 | 1.195–3.308 | 0.0093 |
Resection degree | 76 | 0.3289 | 95 | <0.0001 | ||||
Biopsy vs. Partial | 39 | 1.521 | 0.646–3.579 | 0.3367 | 54 | 7.764 | 3.344–18.170 | <0.0001 |
Biopsy vs. Macroscopic | 47 | 2.113 | 0.848–5.265 | 0.1084 | 61 | 9.925 | 3.900–21.820 | <0.0001 |
Partial vs. Macroscopic | 66 | 1.150 | 0.682–1.940 | 0.5995 | 75 | 1 | 0.598–1.672 | 0.9996 |
RPA | 76 | 0.1596 | 95 | 0.0120 | ||||
≥V vs. <V | 59 | 1.560 | 0.868–2.803 | 0.1367 | 74 | 2.106 | 1.230–3.607 | 0.0066 |
P53 gene status | 76 | 0.7537 | 95 | 0.8356 | ||||
Mutated vs. Non Mutated | 15 | 0.597 | 0.151–2.360 | 0.4622 | 18 | 0.597 | 0.128–2.784 | 0.5118 |
MGMT promoter status | 76 | 0.0834 | 95 | 0.0690 | ||||
Un-Methylated vs. Methylated (All) | 47 | 2.194 | 1.135–4.243 | 0.0195 | 59 | 2.217 | 1.184–4.151 | 0.0129 |
Un-Methylated vs. Methylated (Stupp) | 45 | 2.547 | 1.292–5.021 | 0.0069 | 53 | 2.497 | 1.278–4.880 | 0.0074 |
Un-Methylated vs. Methylated (Completed Stupp) | 31 | 2.083 | 0.926–4.682 | 0.0759 | 35 | 2.062 | 0.872–4.872 | 0.0992 |
Integrin α5 | ||||||||
High vs. Low expression (All) | 76 | 1.696 | 1.031–2.792 | 0.0377 | 95 | 1.598 | 0.998–2.558 | 0.0508 |
High vs. Low expression (Stupp) | 72 | 1.771 | 1.055–2.975 | 0.0307 | 83 | 1.805 | 1.106–3.096 | 0.0191 |
High vs. Low expression (Completed Stupp) | 53 | 1.635 | 0.879–3.040 | 0.1206 | 58 | 2.324 | 1.168–4.621 | 0.0162 |
Variables | PFS | OS | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p * | HR | 95% CI | p * | |
All patients | ||||||
Age (≥60 years vs. <60 years) | 1.38 | 0.51–3.72 | 0.52 | 1.35 | 0.54–3.33 | 0.52 |
Resection degree (low vs. high) | 2.03 | 0.95–4.35 | 0.0683 | 3.72 | 1.60–8.64 | 0.0023 |
RPA (≥V vs. <V) | 1.97 | 0.80–4.86 | 0.14 | 1.43 | 0.61–3.35 | 0.42 |
MGMT (Un-Methylated vs. Methylated) | 4.71 | 1.43–8.93 | 0.0065 | 4.71 | 1.85–11.90 | 0.0011 |
Integrin α5 (high vs. low) | 1.28 | 0.57–2.88 | 0.55 | 1.11 | 0.51–2.40 | 0.79 |
Stupp | ||||||
Age (≥60 years vs. <60 years) | 1.28 | 0.45–3.69 | 0.64 | 1.31 | 0.48–3.60 | 0.58 |
Resection degree (low vs. high) | 1.87 | 0.86–4.07 | 0.12 | 3.73 | 1.52–9.16 | 0.0040 |
RPA (≥V vs. <V) | 1.83 | 0.69–4.88 | 0.22 | 1.71 | 0.45–3.07 | 0.75 |
MGMT (Un-Methylated vs. Methylated) | 4.46 | 1.68–11.84 | 0.0027 | 6.95 | 2.45–19.72 | 0.0002 |
Integrin α5 (high vs. low) | 1.28 | 0.55–3.01 | 0.57 | 1.22 | 0.51–2.91 | 0.66 |
Completed Stupp | ||||||
Age (≥60 years vs. <60 years) | 2.48 | 0.61–10.09 | 0.20 | 2.20 | 0.53–9.09 | 0.27 |
Resection degree (low vs. high) | 1.41 | 0.54–3.68 | 0.48 | 2.04 | 0.60–6.90 | 0.25 |
RPA (≥V vs. <V) | 1.16 | 0.31–4.28 | 0.83 | 3.12 | 0.73–13.25 | 0.12 |
MGMT (Un-Methylated vs. Methylated) | 2.58 | 0.76–8.76 | 0.128 | 4.27 | 1.08–16.83 | 0.038 |
Integrin α5 (high vs. low) | 2.09 | 0.63–6.90 | 0.22 | 4.77 | 1.17–19.44 | 0.029 |
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Etienne-Selloum, N.; Prades, J.; Bello-Roufai, D.; Boone, M.; Sevestre, H.; Trudel, S.; Caillet, P.; Coutte, A.; Desenclos, C.; Constans, J.-M.; et al. Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma. Pharmaceuticals 2021, 14, 882. https://doi.org/10.3390/ph14090882
Etienne-Selloum N, Prades J, Bello-Roufai D, Boone M, Sevestre H, Trudel S, Caillet P, Coutte A, Desenclos C, Constans J-M, et al. Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma. Pharmaceuticals. 2021; 14(9):882. https://doi.org/10.3390/ph14090882
Chicago/Turabian StyleEtienne-Selloum, Nelly, Julien Prades, Diana Bello-Roufai, Mathieu Boone, Henri Sevestre, Stéphanie Trudel, Pascal Caillet, Alexandre Coutte, Christine Desenclos, Jean-Marc Constans, and et al. 2021. "Expression Analysis of α5 Integrin Subunit Reveals Its Upregulation as a Negative Prognostic Biomarker for Glioblastoma" Pharmaceuticals 14, no. 9: 882. https://doi.org/10.3390/ph14090882