CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. CENP-A Clusters in Foci at the Nuclear Periphery in Normal Human Tissue Fixed with AFA
2.2. In Carcinomas CENP-A Clustering and Localization at the Nuclear Periphery Are Altered
2.3. Change in CENP-A Nuclear Localization Pattern as a Marker of Malignancy
2.4. CENP-A Nuclear Localization in Radioresistant and Radiosensitive HNSSC-Derived Cell Line Xenografts
2.5. CENP-A Nuclear Localization Pattern Is Associated with Response to CCRT
2.6. A CENP-A Nuclear Localization Pattern Is a Marker of Predictive Value for Curability of HNSCC Patients by CCRT
3. Discussion
4. Methods
4.1. Tissue Samples
4.2. Immunohistochemistry Imaging
4.3. HNSCC Patients
4.4. Statistical Analysis
5. Conclusions
6. Patent
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | Total (N = 62) | CENP-A Pattern | |||
---|---|---|---|---|---|
C (N = 25) | Non-C (N = 37) | Test | |||
Age (year) | NS | ||||
Median (IQR) | 62 (56–68) | 61 (56–64) | 63 (56–69) | ||
Ki67 (%) | NS | ||||
Median (IQR) | 60 (35–75) | 60 (35–75) | 60 (30–75) | ||
Gender N (%) | NS | ||||
F | 10 (16.1%) | 6 (24%) | 4 (10.8%) | ||
M | 52 (83.9%) | 19 (76%) | 33 (89.2%) | ||
T (TNM) N (%) | 0.06 | ||||
T1 | 4 (6.5%) | 1 (4%) | 3 (8.1%) | ||
T2 | 10 (16.1%) | 4 (16%) | 6 (16.2%) | ||
T3 | 23 (37.1%) | 14 (56%) | 9 (24.3%) | ||
T4 | 25 (40.3%) | 6 (24%) | 19 (51.4%) | ||
N (TNM) N (%) | NS | ||||
N0 | 17 (27.4%) | 8 (32%) | 9 (24.3%) | ||
N1 | 7 (11.3%) | 2 (8%) | 5 (13.5%) | ||
N2a | 3 (4.8%) | 2 (8%) | 1 (2.7%) | ||
N2b | 9 (14.5%) | 5 (20%) | 4 (10.8%) | ||
N2c | 19 (30.6%) | 6 (24%) | 13 (35.1%) | ||
N3 | 7 (11.3%) | 2 (8%) | 5 (13.5%) | ||
Stage | NS | ||||
I | 1 (1.6%) | 1 (4%) | 0 (0%) | ||
II | 3 (4.8%) | 0 (0%) | 3 (8.1%) | ||
III | 18 (29%) | 8 (32%) | 10 (27%) | ||
IV | 40 (64.5%) | 16 (64%) | 24 (64.9%) | ||
Tumor Site N (%) | NS | ||||
Oral cavity | 5 (8.1%) | 3 (12%) | 2 (5.4%) | ||
Oropharynx | 42 (67.7%) | 17 (68%) | 25 (67.6%) | ||
Hypopharynx | 4 (6.5%) | 0 (0%) | 4 (10.8%) | ||
Larynx | 11 (17.7%) | 5 (20%) | 6 (16.2%) | ||
Metastatic Relapse N (%) | 0.025 | ||||
No | 49 (80.3%) | 24 (96%) | 25 (69.4%) | ||
Yes | 12 (19.7%) | 1 (4%) | 11 (30.6%) | ||
NA | 1 | 0 | 1 | ||
HPV N (%) | 0.002 | ||||
HPV- | 27 (43.5%) | 5 (20%) | 22 (59.5%) | ||
HPV+ | 35 (56.5%) | 20 (80%) | 15 (40.5%) | ||
Anisokaryosis | <0.001 | ||||
Mild | 28 (45.2%) | 20 (80%) | 8 (21.6%) | ||
Moderate | 19 (30.6%) | 5 (20%) | 14 (37.8%) | ||
Marked | 15 (24.2%) | 0 (0%) | 15 (40.5%) | ||
CENP-A H-score | 0.003 | ||||
Median (IQR) | 1.6 (1.2–2.7) | 1.8 (1.6–2.7) | 1.5 (0.7–1.8) | ||
Local Disease Control at 2 years | <0.001 | ||||
Yes | 38 (61.3%) | 24 (96%) | 14 (37.8%) | ||
No | 24 (38.7%) | 1 (4%) | 23 (62.2%) |
Univariate Analysis | Multivariate Analysis | ||||||
---|---|---|---|---|---|---|---|
Factors | Category | OR | 95% IC | p -Value | OR | 95% IC | p -Value |
T (TNM) | NS | ||||||
T1/T2 | 1 | ||||||
T3/T4 | 0.56 | [0.1; 1.9] | |||||
N (TNM) | NS | ||||||
N0 | 1 | ||||||
N+ | 0.57 | [0.2; 1.8] | |||||
Stage | |||||||
I/II/III | 1 | NS | |||||
IVa or IVb | 0.46 | [0.1; 1.4] | |||||
HPV status | 0.02 | ||||||
HPV- | 1 | ||||||
HPV+ | 3.61 | [1.3; 11.0] | |||||
Anisokaryosis | |||||||
Mild | 1 | <0.001 | 1 | 0.03 | |||
Moderate | 0.29 | [0.06; 1.1] | 0.74 | [0.14; 3.9] | |||
Marked | 0.03 | [0; 0.1] | 0.11 | [0.01; 0.7] | |||
CENP-A H-score | |||||||
3.1 | [1.5; 7.2] | 0.005 | |||||
CENP-A pattern | 0.001 | 0.002 | |||||
non-C | 1 | 1 | |||||
C | 39.4 | [7.1; 744.0] | 17.6 | [2.6; 362.8] |
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Verrelle, P.; Meseure, D.; Berger, F.; Forest, A.; Leclère, R.; Nicolas, A.; Fortas, E.; Sastre-Garau, X.; Lae, M.; Boudjemaa, S.; et al. CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients. Cancers 2021, 13, 3928. https://doi.org/10.3390/cancers13163928
Verrelle P, Meseure D, Berger F, Forest A, Leclère R, Nicolas A, Fortas E, Sastre-Garau X, Lae M, Boudjemaa S, et al. CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients. Cancers. 2021; 13(16):3928. https://doi.org/10.3390/cancers13163928
Chicago/Turabian StyleVerrelle, Pierre, Didier Meseure, Frédérique Berger, Audrey Forest, Renaud Leclère, André Nicolas, Emilie Fortas, Xavier Sastre-Garau, Marick Lae, Sabah Boudjemaa, and et al. 2021. "CENP-A Subnuclear Localization Pattern as Marker Predicting Curability by Chemoradiation Therapy for Locally Advanced Head and Neck Cancer Patients" Cancers 13, no. 16: 3928. https://doi.org/10.3390/cancers13163928