Table 2.
Multivariate overall survival Cox regression analysis for protein expression of FGFR family members in oral cavity and oropharyngeal squamous cell carcinoma after internal validation by bootstrapping and Bonferroni correction
| Protein (co-)expression | HR | 95 % CI | p | HR | 95 % CI | p |
|---|---|---|---|---|---|---|
| OCSCC (n = 508) | OPSCC (n = 388) | |||||
| FGFR1 | 1.46 | 0.91–2.34 | 0.690 | 1.42 | 0.93–2.16 | 0.648 |
| FGFR2 | 2.03 | 0.64–5.23 | 0.408 | 1.02 | 0.75–1.40 | 1.000 |
| FGFR3 | 1.22 | 0.92–1.63 | 0.966 | 1.09 | 0.79–1.50 | 1.000 |
| FGFR4 | 1.20 | 0.75–1.91 | 1.000 | 1.13 | 0.81–1.57 | 1.000 |
| FGFR1–2 | 1.04 | 0.67–1.61 | 1.000 | 0.71 | 0.31–1.61 | 1.000 |
| FGFR1–4 | 2.44 | 1.29–5.50 | 0.060 | 1.05 | 0.74–1.49 | 1.000 |
| HPV-positive OPSCC (n = 80) | HPV-negative OPSCC (n = 295) | |||||
| FGFR1 | 1.85 | 0.52–6.56 | 1.000 | 1.21 | 0.75–1.93 | 1.000 |
| FGFR2 | 1.23 | 0.38–3.91 | 1.000 | 1.06 | 0.76–1.47 | 1.000 |
| FGFR3 | 1.00 | 0.34–2.94 | 1.000 | 1.16 | 0.82–1.63 | 1.000 |
| FGFR4 | 0.72 | 0.23–2.27 | 1.000 | 0.83 | 0.38–1.82 | 1.000 |
| FGFR1–2 | 35.44 | 4.89–256.84 | 0.006a | 0.30 | 0.09–0.93 | 0.228a |
| FGFR1–4 | 1.03 | 0.34–3.06 | 1.000 | 2.20 | 0.49–9.85 | 1.000 |
Associations between protein expression of FGFR family members and overall survival were analyzed using Cox regression. Significant relationships were further analyzed by multivariate Cox regression models. Covariates and confounders were identified and included in multivariate models. For the relationship between FGFR1–4 protein co-expression and overall survival, postoperative chemotherapy or chemoradiotherapy was identified as an effect modifiers and corrected for in the model. Internal validation of (bio)marker-based risk prediction models was performed by bootstrapping based on 5000 samples Throughout these statistical computations, two-sided p values below 0.05 were considered significant. Cutoff values for protein expression of FGFR family members were optimized on predicting patient outcome. Cutoff values were 10 % for FGFR1, 15 % for FGFR2, +1 intensity for FGFR3 and 33 % for FGFR4. Overall survival status was missing for four oral cavity and two oropharyngeal squamous cell carcinoma patients and HPV status was missing for 13 oropharyngeal squamous cell carcinoma patients. Forty-nine oropharyngeal squamous cell carcinoma patients were excluded from survival analysis because they were treated with palliative intent
95 % CI 95 % confidence interval, FGFR fibroblast growth factor receptor, HPV human papillomavirus, HR hazard ratio, OPSCC oropharyngeal squamous cell carcinoma, OCSCC oral cavity squamous cell carcinoma
aToo few cases were available (FGFR1–2 co-high expression: HPV-positive OPSCC: 2 cases and HPV-negative OPSCC: 3 cases)