Table 2.
Meta-analyses of prognostic and clinicopathological significance of FADD upregulation inNSCC.
| Pooled Data | Heterogeneity | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Meta-Analyses | No. of Studies | No. of Patients |
Stat. Model | Wt | ES (95% CI) | p-Value | Phet |
I2 (%) |
Appendix a |
| SURVIVAL PARAMETERS | |||||||||
| Overall survival | |||||||||
| All b | 7 * | 1198 * | REM | D-L | HR = 1.45 (1.16–1.81) | 0.001 | <0.001 | 74.3 | FigureS3, p10 |
| Subgroup analysis by alteration c | |||||||||
| FADD amplification | 1 | 339 | ── | ── | HR = 1.53 (1.10–2.12) | 0.01 | ── | ── | FigureS3, p10 |
| pFADD overexpression | 3 | 285 | REM | D-L | HR = 1.14 (0.82–1.56) | 0.44 | 0.15 | 46.9 | FigureS3, p10 |
| FADD overexpression | 7 | 1196 | REM | D-L | HR = 1.52 (1.28–1.81) | <0.001 | 0.50 | 0.0 | FigureS3, p10 |
| Subgroup analysis by geographical area (FADD overexpression group) c | |||||||||
| Asian | 2 | 587 | REM | D-L | HR = 1.66 (1.05–2.63) | 0.03 | 0.15 | 52.9 | FigureS4, p11 |
| Non-Asian | 5 | 609 | REM | D-L | HR = 1.51 (1.20–1.90) | <0.001 | 0.52 | 0.0 | FigureS4, p11 |
| Subgroup analysis by affected site (FADD overexpression group) c | |||||||||
| LSCC | 3 | 290 | REM | D-L | HR = 1.40 (1.06–1.85) | 0.02 | 0.39 | 0.0 | FigureS5, p12 |
| OSCC | 1 | 339 | ── | ── | HR = 1.39 (1.03–1.87) | 0.03 | ── | ── | FigureS5, p12 |
| NPSCC | 1 | 248 | ── | ── | HR = 2.27 (1.26–4.09) | 0.006 | ── | ── | FigureS5, p12 |
| HNSCC mixed | 2 | 319 | REM | D-L | HR = 1.77 (1.18–2.65) | 0.005 | 0.50 | 0.0 | FigureS5, p12 |
| Subgroup analysis by anti-FADD antibody (FADD overexpression group) c | |||||||||
| A66-2 | 4 | 512 | REM | D-L | HR = 1.53 (1.18–1.97) | 0.001 | 0.36 | 7.3 | FigureS6, p13 |
| H181 | 3 | 684 | REM | D-L | HR = 1.54 (1.18–2.01) | 0.002 | 0.34 | 6.9 | FigureS6, p13 |
| Subgroup analysis by immunohistochemical pattern (FADD overexpression group) c | |||||||||
| Cytoplasmic | 2 | 189 | REM | D-L | HR = 1.58 (0.87–2.88) | 0.13 | 0.65 | 0.0 | FigureS7, p14 |
| Nuclear and cytoplasmic | 5 | 1007 | REM | D-L | HR = 1.54 (1.25–1.91) | <0.001 | 0.27 | 22.5 | FigureS7, p14 |
| Univariable meta-regression d | |||||||||
| Sex (% of males) | 7 | 1196 | random-effects meta-regression |
Coef = −0.003 (−0.027 to 0.021) |
0.729 ± 0.004 e | ── | ── | FigureS8, p15 | |
| Age (mean age of patients) | 7 | 1196 | random-effects meta-regression |
Coef = −0.008 (−0.052 to 0.035) |
0.704 ±0.004 e | ── | ── | FigureS9, p16 | |
| Stage (% of stage-III/IV patients) | 7 | 1196 | random-effects meta-regression |
Coef = 0.003 (−0.007 to 0.013) |
0.558 ± 0.005 e | ── | ── | FigureS10, p17 | |
| Follow up period (months) | 7 | 1196 | random-effects meta-regression |
Coef = −0.001 (−0.005 to 0.004) |
0.769 ± 0.004 e | ── | ── | FigureS11, p18 | |
| Disease-specific survival | |||||||||
| All b | 3 * | 422 * | REM | D-L | HR=2.63 (1.76–3.92) | <0.001 | 0.56 | 0.0 | FigureS12, p19 |
| Subgroup analysis by alteration c | |||||||||
| pFADD overexpression | 1 | 133 | ── | ── | HR = 3.05 (1.29–7.22) | 0.01 | ── | ── | FigureS12, p19 |
| FADD overexpression | 3 | 422 | REM | D-L | HR = 2.52 (1.61–3.96) | <0.001 | 0.73 | 0.0 | FigureS12, p19 |
| Disease-free survival | |||||||||
| All b | 3 * | 658 * | REM | D-L | HR = 1.57 (1.28–1.94) | <0.001 | 0.53 | 0.0 | FigureS13, p20 |
| Subgroup analysis by alteration c | |||||||||
| FADD amplification | 1 | 339 | ── | ── | HR = 1.39 (0.96–2.02) | 0.08 | ── | ── | FigureS13, p20 |
| FADD overexpression | 3 | 658 | REM | D-L | HR = 1.67 (1.29–2.15) | <0.001 | 0.45 | 0.0 | FigureS13, p20 |
| Local recurrence | |||||||||
| All b | 2 * | 152 * | REM | D-L | Data not pooled | 0.21 | 0.03 | 67.3 | ── |
| Subgroup analysis by alteration c | |||||||||
| pFADD overexpression | 2 | 152 | REM | D-L | Data not pooled | 0.41 | 0.02 | 81.6 | Manuscript, Figure 4 |
| FADD overexpression | 2 | 150 | REM | D-L | Data not pooled | 0.45 | 0.06 | 70.7 | |
| CLINICO-PATHOLOGICAL CHARACTERISTICS | |||||||||
| T status | |||||||||
| All b | 3* | 727 * | REM | D-L | OR = 0.83 (0.63–1.08) | 0.17 | 0.57 | 0.0 | FigureS14, p21 |
| Subgroup analysis by alteration c | |||||||||
| FADD amplification | 1 | 339 | ── | ── | OR = 1.07 (0.63–1.82) | 0.79 | ── | ── | FigureS14, p21 |
| FADD overexpression | 3 | 727 | REM | D-L | OR = 0.76 (0.55–1.03) | 0.08 | 0.67 | 0.0 | FigureS14, p21 |
| N status | |||||||||
| All b | 10* | 1649 * | REM | D-L | OR = 2.07 (1.47–2.91) | <0.001 | 0.008 | 55.2 | |
| Subgroup analysis by alteration c | |||||||||
| FADD amplification | 3 | 533 | REM | D-L | OR = 2.30 (1.16–4.58) | 0.02 | 0.18 | 41.1 | Manuscript, Figure 2 |
| pFADD overexpression | 1 | 59 | ── | ── | OR = 1.02 (0.27–3.83) | 0.98 | ── | ── | |
| FADD overexpression | 9 | 1483 | REM | D-L | OR = 2.07 (1.34–3.20) | 0.001 | 0.005 | 63.3 | |
| Sensitivity analysis | |||||||||
| All f | 9 * | 1609 * | REM | D-L | OR = 2.36 (1.85–3.00) | <0.001 | 0.27 | 17.9 | FigureS16, p23 |
| Sensitivity analysis stratified by alteration f | |||||||||
| FADD amplification | 3 | 533 | REM | D-L | OR = 2.30 (1.16–4.58) | 0.02 | 0.18 | 41.1 | FigureS16, p23 |
| pFADD overexpression | 1 | 59 | ── | ── | OR = 1.02 (0.27–3.83) | 0.98 | ── | ── | FigureS16, p23 |
| FADD overexpression | 8 | 1443 | REM | D-L | OR = 2.42 (1.84–3.18) | <0.001 | 0.30 | 16.3 | FigureS16, p23 |
| Clinical stage | |||||||||
| All b | 7 * | 812 * | REM | D-L | OR = 1.74 (1.26–2.41) | 0.001 | 0.44 | 0.0 | FigureS17, p24 |
| Subgroup analysis by alteration c | |||||||||
| FADD amplification | 3 | 224 | REM | D-L | OR = 1.92 (0.73–5.06) | 0.18 | 0.20 | 38.3 | FigureS17, p24 |
| pFADD overexpression | 1 | 59 | ── | ── | OR = 1.02 (0.27–3.83) | 0.98 | ── | ── | FigureS17, p24 |
| FADD overexpression | 5 | 616 | REM | D-L | OR = 1.72 (1.17–2.51) | 0.005 | 0.44 | 0.0 | FigureS17, p24 |
| Histological grade | |||||||||
| All b | 3 * | 439 * | REM | D-L | Data not pooled | 0.02 | 0.10 | 48.7 | ── |
| Subgroup analysis by alteration c | |||||||||
| FADD amplification | 2 | 369 | REM | D-L | Data not pooled | 0.17 | 0.04 | 76.2 | Manuscript, Figure 4 |
| FADD overexpression | 3 | 439 | REM | D-L | Data not pooled | 0.22 | 0.18 | 41.0 | |
Abbreviations: Stat., statistical; Wt, method of weighting; ES, estimation; CI, confidence intervals; REM, random-effects model; D-L, DerSimonian and Laird method; LSCC, laryngeal squamous cell carcinoma; OSCC, oral squamous cell carcinoma; NPSCC, nasopharyngeal squamous cell carcinoma; HNSCC, head and neck squamous cell carcinomas; OR, odds ratio; HR, hazard ratio. * More than one alteration was analyzed per study. a—More information in the appendix, b—Prognosis meta-analyses, c—Prognosis meta-analyses (Subgroup analyses), d—Effect of study covariates on overall survival and FADD overexpression among patients with HNSCC, e—p-value ± standard error after 10,000 permutations based on Montecarlo simulations, f—“Leave-one-out” method. Haili et al. 2010—identified as an outlier and main source of heterogeneity- was omitted from N status meta-analysis (see also Figure 3).