Introduction
Materials and methods
Study population
Demographic and clinical data
SNP selection and genotyping
Statistical analysis
Results
Distribution of patients characteristics and prognosis analysis
Variable | No. of total patients (%) | Overall survival | Recurrence-free survival | ||||
---|---|---|---|---|---|---|---|
No. of deaths (%) | HR (95 % CI)a
|
P value | No. of recurrences (%) | HR (95 % CI)a
|
P value | ||
Age | |||||||
≤59 | 244 (49.4) | 71 (47.7) | Ref. | 110 (52.6) | Ref. | ||
>59 | 250 (50.6) | 78 (52.3) | 0.89 (0.63–1.25) | 0.503 | 99 (47.4) | 0.84 (0.63–1.11) | 0.217 |
Gender | |||||||
Female | 109 (22.1) | 32 (21.5) | Ref. | 50 (23.9) | Ref. | ||
Male | 385 (77.9) | 117 (78.5) | 1.07 (0.61–1.87) | 0.826 | 159 (76.1) | 1.16 (0.72–1.87) | 0.532 |
Smoking status | |||||||
Never smoker | 154 (31.2) | 45 (30.2) | Ref. | 70 (33.5) | Ref. | ||
Ever smoker | 340 (68.8) | 104 (69.8) | 0.94 (0.57–1.56) | 0.812 | 139 (66.5) | 0.77 (0.50–1.17) | 0.224 |
Histology | |||||||
Squamous cell carcinoma | 270 (54.7) | 79 (53.0) | Ref. | 109 (52.2) | Ref. | ||
Adenocarcinoma | 149 (30.2) | 33 (22.1) | 0.59 (0.38–0.92) | 0.020 | 57 (26.8) | 0.74 (0.52–1.06) | 0.108 |
Othersb
| 75 (15.1) | 37 (24.8) | 1.54 (0.91–2.59) | 0.106 | 44 (21.1) | 1.22 (0.78–1.93) | 0.375 |
TNM Stage | |||||||
I/II | 287 (58.1) | 74 (48.7) | Ref. | 98 (46.9) | Ref. | ||
III | 207 (41.9) | 78 (51.3) | 1.85 (1.33–2.57) | <0.001 | 111 (53.1) | 1.94 (1.47–2.56) | <0.001 |
T-stage | |||||||
T1/2 | 306 (61.9) | 80 (53.7) | Ref. | 117 (56.0) | Ref. | ||
T3/4 | 188 (38.1) | 69 (46.3) | 1.41 (0.98–2.05) | 0.067 | 92 (44.0) | 1.24 (0.90–1.70) | 0.184 |
N-stage | |||||||
N0 | 231 (46.8) | 60 (40.3) | Ref. | 77 (36.8) | Ref. | ||
N1/2/3 | 263 (53.2) | 89 (59.7) | 1.45 (0.87–2.44) | 0.161 | 132 (63.2) | 1.60 (1.05–2.46) | 0.032 |
Differentiation | |||||||
Well/moderate | 345 (69.8) | 85 (57.0) | Ref. | 125 (59.8) | Ref. | ||
Poorly/undifferentiated | 149 (30.2) | 64 (43.0) | 1.35 (0.89–2.07) | 0.163 | 84 (40.2) | 1.56 (1.10–2.22) | 0.013 |
Adjuvant therapy | |||||||
No | 129 (26.1) | 45 (30.2) | Ref. | 52 (24.9) | Ref. | ||
Yes | 365 (73.9) | 104 (69.8) | 0.44 (0.31–0.63) | <0.001 | 157 (75.1) | 0.72 (0.53–0.99) | 0.040 |
Association of HIF1A SNPs with clinical outcomes in NSCLC patients
SNP | Patient subgroup | Genotypes | Overall survival | Recurrence-free survival | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Death/total | HR (95 % CI)a
|
P value | No. times in bootstrapb sample P < 0.05 | Recurrence/total | HR (95 % CI)a
|
P value | No. times in bootstrapb sample P < 0.05 | |||
rs2057482 | Stage I+II | CC | 60/200 | Ref. | 75/200 | Ref. | ||||
CT+TT | 12/86 | 0.42 (0.22–0.80) | 0.008 | 100 | 22/86 | 0.60 (0.36–0.97) | 0.039 | 62 | ||
Stage III | CC | 50/144 | Ref. | 79/144 | Ref. | |||||
CT+TT | 26/61 | 1.54 (0.94–2.53) | 0.087 | 31/61 | 0.93 (0.60–1.44) | 0.735 | ||||
rs2301113 | Stage I+II | AA | 38/130 | Ref. | 49/130 | Ref. | ||||
AC+CC | 34/156 | 0.71 (0.44–1.15) | 0.165 | 48/156 | 0.77 (0.51–1.16) | 0.206 | ||||
Stage III | AA | 34/89 | Ref. | 52/89 | Ref. | |||||
AC+CC | 42/117 | 1.04 (0.66–1.65) | 0.866 | 58/117 | 0.89 (0.61–1.32) | 0.569 |
Association of HIF1A SNPs with clinical outcomes in different T-stage or N-stage disease
SNP | Variables | Genotypes | Overall survival | Recurrence-free survival | ||||
---|---|---|---|---|---|---|---|---|
Death/total | HR (95 % CI)a
|
P value | Recurrence/total | HR (95 % CI)a
|
P value | |||
rs2057482 | T1+T2 | CC | 59/202 | Ref. | 85/202 | Ref. | ||
CT+TT | 21/103 | 0.60 (0.36–1.00) | 0.050 | 31/103 | 0.59 (0.39–0.90) | 0.015 | ||
T3+T4 | CC | 51/142 | Ref. | 69/142 | Ref. | |||
CT+TT | 17/44 | 1.39 (0.78–2.46) | 0.263 | 22/44 | 1.15 (0.70–1.91) | 0.576 | ||
N0 | CC | 52/159 | Ref. | 62/159 | Ref. | |||
CT+TT | 8/72 | 0.34 (0.16–0.73) | 0.005 | 15/72 | 0.49 (0.27–0.86) | 0.014 | ||
N1+N2+N3 | CC | 58/185 | Ref. | 92/185 | Ref. | |||
CT+TT | 30/75 | 1.34 (0.85–2.11) | 0.209 | 38/75 | 1.02 (0.69–1.51) | 0.921 | ||
rs2301113 | T1+T2 | AA | 43/132 | Ref. | 61/132 | Ref. | ||
AC+CC | 37/173 | 0.60 (0.38–0.93) | 0.023 | 55/173 | 0.61 (0.42–0.89) | 0.010 | ||
T3+T4 | AA | 29/87 | Ref. | 40/87 | Ref. | |||
AC+CC | 39/100 | 1.37 (0.84–2.26) | 0.210 | 51/100 | 1.34 (0.88–2.04) | 0.176 | ||
N0 | AA | 35/110 | Ref. | 43/110 | Ref. | |||
AC+CC | 25/121 | 0.61 (0.36–1.03) | 0.063 | 34/121 | 0.67 (0.42–1.06) | 0.084 | ||
N1+N2+N3 | AA | 37/109 | Ref. | 58/109 | Ref. | |||
AC+CC | 51/152 | 1.02 (0.67–1.57) | 0.922 | 72/152 | 0.93 (0.66–1.33) | 0.697 |