Genomic Signature of Oral Squamous Cell Carcinomas from Non-Smoking Non-Drinking Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Patient Clinical Characteristics and HPV Status
3.2. Genomic Alterations and Clinical Associations for OSCC Patients
3.3. Mutation Differences between NSND and SD Patients
4. Discussion
5. Conclusions
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 | All Patients (n = 176) | |
---|---|---|
Gender | Female | 76 (43.2) |
Male | 100 (56.8) | |
Age | Median (range) | 66 (33–98) |
Non-smoker | 86 (48.9) | |
Non-drinker | 79 (44.9) | |
NSND | 59 (33.5) | |
T stage | 1 | 39 (22.2) |
2 | 66 (37.5) | |
3 | 14 (8.0) | |
4 | 57 (32.4) | |
N stage | N0 | 115 (65.3) |
N+ | 61 (34.7) | |
AJCC stage | I | 32 (18.2) |
II | 50 (28.4) | |
III | 37 (21.0) | |
IV | 57 (32.4) | |
Perineural invasion | Present | 32 (18.2) |
Absent | 144 (81.8) | |
Lymphovascular invasion | Present | 18 (10.2) |
Absent | 158 (89.8) | |
Extracapsular spread | Present | 20 (11.4) |
Absent | 156 (88.6) | |
HPV status | Positive | 3 (1.7) |
Negative | 173 (98.3) | |
Radiotherapy | Yes | 110 (62.5) |
No | 66 (37.5) | |
Chemotherapy | Yes | 39 (22.2) |
No | 137 (77.8) |
Group 1 vs. Group 2 | Gene | Group 1 n (%) | Group 2 n (%) | OR (95% CI) | p |
---|---|---|---|---|---|
Male vs. Female | TP53 mut | 67/100 (67.0) | 39/76 (51.3) | 1.9 (1.0–3.7) | 0.043 * |
CASP8 mut | 3/100 (3.0) | 11/76 (14.5) | 0.2 (0.0–0.7) | 0.009 * | |
Smokers vs. Non-smokers | CDKN2A mut | 15/90 (16.7) | 27/86 (31.4) | 0.4 (0.2–0.9) | 0.033 * |
Drinkers vs. Non-drinkers | CASP8 mut | 4/97 (4.1) | 10/79 (12.7) | 0.3 (0.1–1.1) | 0.050 * |
LAMA4 mut | 1/97 (1.0) | 8/79 (10.1) | 0.1 (0.0–0.7) | 0.012 * | |
NSND vs. SD | CDKN2A mut | 21/59 (35.6) | 21/117 (17.9) | 2.5 (1.2–5.5) | 0.014 * |
EGFR amp | 10/59 (16.9) | 6/117 (5.1) | 3.7 (1.2–13.3) | 0.023 * | |
BRCA2 del | 7/59 (11.9) | 2/117 (1.7) | 7.6 (1.4–77.8) | 0.007 * | |
T3/4 tumours vs. T1/2 tumours | CDKN2A mut | 26/71 (36.6) | 16/105 (15.2) | 3.2 (1.5–7.1) | 0.002 * |
CDKN2A del | 7/71 (9.9) | 0/105 (0) | Inf (2.3–Inf) | 0.001 * | |
BRCA2 del | 8/71 (11.3) | 1/105 (1.0) | 13 (1.7–590.0) | 0.003 * | |
LN+ vs. LN− | TP53 mut | 48/61 (78.7) | 58/115 (50.4) | 3.6 (1.7–8.1) | <0.001 * |
BRCA2 del | 7/61 (11.5) | 2/115 (1.7) | 7.2 (1.3–73.5) | 0.009 * | |
LVI+ vs. LVI− | TP53 mut | 15/18 (83.3) | 91/158 (57.6) | 3.7 (1.0–20.0) | 0.042 * |
NCOR2 mut | 4/18 (22.2) | 8/156 (5.1) | 5.3 (1.0–22.9) | 0.023 * | |
PNI+ vs. PNI− | EGFR amp | 7/32 (21.9) | 9/144 (6.2) | 4.2 (1.2–13.9) | 0.012 * |
ECS+ vs. ECS− | CDKN2A mut | 9/20 (45.0) | 33/156 (21.2) | 3 (1.0–8.8) | 0.026 * |
TP53 mut | 19/20 (95.0) | 87/156 (55.8) | 15 (2.3–633.0) | <0.001 * | |
EGFR amp | 5/20 (25.0) | 11/156 (7.1) | 4.3 (1.0–16.0) | 0.022 * | |
BRCA2 del | 4/20 (20.0) | 5/156 (3.2) | 7.4 (1.3–38.4) | 0.011 * |
Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
HR | 95% CI | p | AHR | 95% CI | p | |
PIK3CA Mutation | 2.0 | 1.0–3.9 | 0.050 * | 1.4 | 0.7–2.9 | 0.303 |
Male vs. female | 0.8 | 0.5–1.3 | 0.406 | 1.1 | 0.6–1.9 | 0.808 |
Age (in decades) | 1.7 | 1.2–1.8 | <0.001 * | 1.6 | 1.3–2.0 | <0.001 * |
NSND vs. SD | 1.7 | 1.0–2.8 | 0.050 * | 1.2 | 0.6–2.1 | 0.630 |
T3/4 vs. T1/2 | 2.9 | 1.7–5.0 | <0.001 * | 2.6 | 1.5–4.4 | 0.001 * |
LN+ vs. LN- | 2.3 | 1.4–3.8 | 0.001 * | 2.0 | 1.1–3.6 | 0.019 * |
PNI+ vs. PNI- | 1.7 | 1.0–3.1 | 0.064 | 1.5 | 0.8–2.7 | 0.211 |
LVI+ vs. LVI- | 2.0 | 1.0–4.0 | 0.064 | 1.4 | 0.6–3.1 | 0.443 |
EGFR Amplification | 2.7 | 1.4–5.4 | 0.004 * | 1.8 | 0.9–3.6 | 0.118 |
Male vs. female | 0.8 | 0.5–1.3 | 0.406 | 1.1 | 0.6–1.9 | 0.861 |
Age (in decades) | 1.7 | 1.2–1.8 | <0.001 * | 1.6 | 1.3–2.1 | <0.001 * |
NSND vs. SD | 1.7 | 1.0–2.8 | 0.050 * | 1.1 | 0.6–2.0 | 0.829 |
T3/4 vs. T1/2 | 2.9 | 1.7–5.0 | <0.001 * | 2.4 | 1.4–4.2 | 0.001 * |
LN+ vs. LN- | 2.3 | 1.4–3.8 | 0.001 * | 2.0 | 1.1–3.7 | 0.016 * |
PNI+ vs. PNI- | 1.7 | 1.0–3.1 | 0.064 | 1.4 | 0.7–2.6 | 0.301 |
LVI+ vs. LVI- | 2.0 | 1.0–4.0 | 0.064 | 1.5 | 0.6–3.3 | 0.360 |
CDKN2A Deletion | 2.8 | 1.1–7.1 | 0.026 * | 1.8 | 0.6–5.0 | 0.261 |
Male vs. female | 0.8 | 0.5–1.3 | 0.406 | 1.0 | 0.6–1.9 | 0.932 |
Age (in decades) | 1.7 | 1.2–1.8 | <0.001 * | 1.6 | 1.3–2.0 | <0.001 * |
NSND vs. SD | 1.7 | 1.0–2.8 | 0.050 * | 1.2 | 0.6–2.3 | 0.556 |
T3/4 vs. T1/2 | 2.9 | 1.7–5.0 | <0.001 * | 2.3 | 1.3–4.1 | 0.004 * |
LN+ vs. LN- | 2.3 | 1.4–3.8 | 0.001 * | 2.2 | 1.2–4.1 | 0.009 * |
PNI+ vs. PNI- | 1.7 | 1.0–3.1 | 0.064 | 1.5 | 0.8–2.8 | 0.172 |
LVI+ vs. LVI- | 2.0 | 1.0–4.0 | 0.064 | 1.2 | 0.5–2.8 | 0.654 |
Alteration | SD (n = 117, 434 Mutations) | NSND, All (n = 59, 366 Mutations) | NSND, Low Mutation Group (n = 54, 233 Mutations) | NSND, High Mutation Group (n = 5, 133 Mutations) |
---|---|---|---|---|
C > A | 60 (13.8) | 39 (10.7) | 27 (11.6) | 12 (9.6) |
C>G | 44 (10.1) | 42 (11.5) | 27 (11.6) | 15 (12.0) |
C>T | 178 (41.0) | 164 (44.8) | 107 (45.9) | 57 (45.6) |
T>A | 33 (7.6) | 12 (3.3) | 6 (2.6) | 6 (4.8) |
T > C | 47 (10.8) | 61 (16.7) | 35 (15.0) | 26 (20.8) |
T>G | 18 (4.1) | 16 (4.4) | 7 (3.0) | 9 (7.2) |
Indel | 54 (12.4) | 32 (8.7) | 24 (10.3) | 8 (6.0) |
Compared to SD | p = 0.010 * | p = 0.067 | p = 0.019 * | |
Compared to NSND | p = 0.297 |
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Koo, K.; Mouradov, D.; Angel, C.M.; Iseli, T.A.; Wiesenfeld, D.; McCullough, M.J.; Burgess, A.W.; Sieber, O.M. Genomic Signature of Oral Squamous Cell Carcinomas from Non-Smoking Non-Drinking Patients. Cancers 2021, 13, 1029. https://doi.org/10.3390/cancers13051029
Koo K, Mouradov D, Angel CM, Iseli TA, Wiesenfeld D, McCullough MJ, Burgess AW, Sieber OM. Genomic Signature of Oral Squamous Cell Carcinomas from Non-Smoking Non-Drinking Patients. Cancers. 2021; 13(5):1029. https://doi.org/10.3390/cancers13051029
Chicago/Turabian StyleKoo, Kendrick, Dmitri Mouradov, Christopher M. Angel, Tim A. Iseli, David Wiesenfeld, Michael J. McCullough, Antony W. Burgess, and Oliver M. Sieber. 2021. "Genomic Signature of Oral Squamous Cell Carcinomas from Non-Smoking Non-Drinking Patients" Cancers 13, no. 5: 1029. https://doi.org/10.3390/cancers13051029