Background
Methods
Patients
Immunohistochemical detection
SNP selection and genotyping
Cell culture and siRNA transfection
Quantitative RT-PCR assay
Cell proliferation
Cell migration and invasion
Statistical analysis
Results
Associations between SLC39A6 rs1050631 genotype and clinico-demographic characteristics
Variables | Patients N (%) | SLC39A6 rs1050631 genotype (N) | P* | Pdominant a | Padditive b | ||
---|---|---|---|---|---|---|---|
TT(%) | CT(%) | CC(%) | |||||
Total | 512 | 20 (3.9) | 139 (27.1) | 353 (69.0) | |||
Age | 0.26 | 0.25 | 0.14 | ||||
< 60 | 235 (45.9) | 6 (1.2) | 61 (11.9) | 168 (32.8) | |||
≥ 60 | 277 (54.1) | 14 (2.7) | 78 (15.2) | 185 (36.1) | |||
Gender | 0.38 | 0.18 | 0.25 | ||||
Male | 383 (74.8) | 15 (2.9) | 110 (21.5) | 258 (50.4) | |||
Female | 129 (25.2) | 5 (1.0) | 29 (5.7) | 95 (18.5) | |||
Grade of differentiation | 0.85 | 0.93 | 0.86 | ||||
Well differentiated | 21 (4.1) | 1 (0.2) | 6 (1.2) | 14 (2.7) | |||
Moderately differentiated | 263 (51.4) | 9 (1.8) | 75 (14.6) | 179 (35.0) | |||
Poorly differentiated | 228 (44.5) | 10 (2.0) | 58 (11.3) | 160 (31.2) | |||
Gross findings | 0.79 | 0.96 | 0.81 | ||||
Apophysis | 35 (6.8) | 2 (0.4) | 9 (1.8) | 24 (4.7) | |||
Invasion | 477 (93.2) | 18 (3.5) | 130 (25.4) | 329 (64.3) | |||
Lauren classification | 0.65 | 0.45 | 0.22 | ||||
Intestinal type | 420 (82.1) | 18 (3.5) | 119 (23.2) | 283 (55.3) | |||
Diffuse type | 81 (15.8) | 2 (0.4) | 18 (3.5) | 61((11.9)) | |||
Uncertain type | 11 (2.1) | 0 (0) | 2 (0.4) | 9 (1.8) | |||
Tumor location | 0.32 | 0.38 | 0.42 | ||||
Upper third | 179 (35.0) | 4 (0.8) | 52 (10.2) | 123 (24.0) | |||
Middle third | 78 (15.2) | 4 (0.8) | 16 (3.1) | 58 (11.3) | |||
Lower third | 252 (49.2) | 12 (2.3) | 69 (13.5) | 171 (33.4) | |||
Total | 3 (0.6) | 0 (0) | 2 (0.4) | 1 (0.2) | |||
Tumor size | 0.99 | 0.88 | 0.92 | ||||
≥ 5 cm | 210 (41.0) | 8 (1.6) | 58 (11.3) | 144 (28.1) | |||
< 5 cm | 302 (59.0) | 12 (2.3) | 81 (15.8) | 209 (40.8) | |||
Survival | 0.002 | < 0.001 | < 0.001 | ||||
Alive | 182 (35.5) | 4 (0.4) | 35 (6.8) | 143 (27.9) | |||
Dead | 330 (64.5) | 16 (3.1) | 104 (20.3) | 210 (41.0) | |||
Recurrence | 0.004 | < 0.001 | < 0.001 | ||||
Yes | 334 (65.2) | 16 (3.1) | 104 (20.3) | 214 (41.8) | |||
No | 178 (34.8) | 4 (0.8) | 35 (6.8) | 139 (27.1) | |||
Distant metastasis | 0.43 | 0.87 | 0.81 | ||||
Yes | 63 (12.3) | 4 (0.8) | 15 (2.9) | 44 (8.6) | |||
No | 449 (87.7) | 16 (3.1) | 124 (24.2) | 309 (60.4) | |||
Lymph node metastasis | 0.12 | 0.21 | 0.08 | ||||
Yes | 398 (77.7) | 19 (3.7) | 110 (21.5) | 269 (52.5) | |||
No | 114 (22.3) | 1 (0.2) | 29 (5.7) | 84 (16.4) | |||
Chemotherapy | |||||||
Yes | 329 (64.3) | 13 (2.5) | 93 (18.2) | 223 (43.6) | 0.61 | 0.78 | 0.69 |
No | 183 (35.7) | 7 (1.4) | 46 (9.0) | 130 (25.4) |
Associations between SLC39A6 rs1050631 genotype and GA recurrence
SNP | Genotype | Recurrence | Unadjusted | Adjusteda | ||||
No(n)/Yes(n) | HR | 95%CI | p | HR | 95%CI | p | ||
Total (n = 512) | 178/334 | |||||||
rs1050631 | CC | 139/214 | 1(reference) | 1(reference) | ||||
CT | 35/104 | 1.813 | 1.09–3.01 | 0.022 | 1.379 | 1.090–1.744 | 0.007 | |
TT | 4/16 | 1.400 | 1.11–1.77 | 0.005 | 1.441 | 0.864–2.403 | 0.161 | |
CT + TT | 39/120 | 1.440 | 1.15–1.80 | 0.001 | 1.387 | 1.108–1.735 | 0.004 | |
SNP | Genotype | Survival | Unadjusted | Adjusteda | ||||
Ali(n)/Dea(n) | HR | 95%CI | p | HR | 95%CI | p | ||
Total(n = 512) | 182/330 | |||||||
rs1050631 | CC | 143/210 | 1(reference) | 1(reference) | ||||
CT | 35/104 | 1.440 | 1.138–1.823 | 0.002 | 1.416 | 1.119–1.792 | 0.004 | |
TT | 4/16 | 1.947 | 1.170–3.239 | 0.010 | 1.523 | 0.912–2.542 | 0.107 | |
CT + TT | 39/120 | 1.492 | 1.192–1.868 | < 0.001 | 1.429 | 1.141–1.790 | 0.002 |
Associations between SLC39A6 rs1050631 genotype and overall survival
SLC39A6 overexpression in GA
SLC39A6 knockdown inhibits proliferation, migration and invasion of GA cells
Association of different genotype at SLC39A6 rs1050631 with SLC39A6 expression in GA
SNP | Genotype | expression of SLC39A6 | Case-totala | Case-caseb | |
---|---|---|---|---|---|
Low(n)/ High(n) | High expression rate (%) | p < 0.00833 | p < 0.0125 | ||
Total(n = 198) | 112/86 | 43.4 | |||
rs1050631 | CC | 61/31 | 33.7 | 0.116 | 1vs2:0.005 |
CT | 42/50 | 54.3 | 0.083 | 2vs3:0.422 | |
TT | 8/6 | 42.9 | 0.966 | 1vs3:0.712 |