Expression status of SYTs family members in GC
We explored the mRNA expression levels of SYTs family members from 375 cases of GC and 32 normal controls, which originated from TCGA database. As shown in Fig. 1, SYT4, SYT9, SYT13 and SYT14 were significantly upregulated in GC samples compared to normal control (P = 0.022, P = 0.023, P < 0.001 and P = 0.037, respectively), while SYT8, SYT10, SYT12, SYT15 and SYT16 were significantly downregulated in GC samples (P < 0.001, P < 0.001, P = 0.00083, P = 0.00062 and P = 0.00083, respectively). However, there were not significantly different in SYT1, SYT2, SYT3, SYT5, SYT6, SYT7, SYT11 and SYT17 expressions compared GC samples with normal controls (P = 0.53, P = 0.46, P = 0.92, P = 0.093, P = 0.84, P = 0.43, P = 0.99 and P = 0.28, respectively).
Validation the prognostic value of SYTs family members in GC
Subsequently, we utilized Kaplan-Meier survival analysis to evaluate the prognostic values between SYTs family members and overall survival (OS) and progression-free survival (PFS) in patients with GC from TCGA database. We discovered that the high expression of SYT3, SYT4, SYT9 and SYT14 was associated with worse OS (P = 0.026, P = 0.046, P = 0.046 and P = 0.002, respectively), whereas the expression levels of SYT1, SYT2, SYT5, SYT6, SYT7, SYT8, SYT10, SYT11, SYT12, SYT13, SYT15, SYT16 and SYT17 were not correlated with OS for the patients with GC (P = 0.248, P = 0.897, P = 0.585, P = 0.248, P = 0.748, P = 0.164, P = 0.778, P = 0.662, P = 0.115, P = 0.221, P = 0.064, P = 0.414 and P = 0.794, respectively) (Fig. 2). Moreover, we found that up-regulated SYT4, SYT9 and SYT14 was significantly correlated with worse PFS (P = 0.032, P = 0.007 and P < 0.001, respectively), whereas the expression levels of SYT1, SYT2, SYT3, SYT5, SYT6, SYT7, SYT8, SYT10, SYT11, SYT12, SYT13, SYT15, SYT16 and SYT17 were not associated with PFS for the patients with GC (P = 0.994, P = 0.059, P = 0.124, P = 0.094, P = 0.182, P = 0.611, P = 0.514, P = 0.289, P = 0.141, P = 0.08, P = 0.398, P = 0.069, P = 0.051 and P = 0.064) (Fig. 3).
Prognostic value of SYTs family members for assessing overall survival in GC
Based on the above-mentioned results, we obtained the SYT4, SYT9 and SYT14 as candidate genes for further research in GC. Then, we utilized receiver operating characteristic curve (ROC) to evaluate the capabilities of SYT4, SYT9 and SYT14 predicting OS for patients with GC at 1-year, 3-year and 5-year. The area under curve (AUC) values of SYT4, SYT9 and SYT14 were 0.606, 0.603 and 0.564, respectively, at 1-year. Moreover, the AUC values of SYT4, SYT9 and SYT14 were 0.538, 0.626 and 0.570, respectively, at 3-year. Furthermore, the AUC values of SYT4, SYT9 and SYT14 were 0.500, 0.590 and 0.671, respectively, at 5-year (Fig. 4).
Correlation of SYTs family members expression and methylation in GC
Methylation of DNA promoter regions is one of crucial factors that regulates gene expression during the pathogenesis of human cancer. Then, we observed the methylation cg sites of SYT4, SYT9 and SYT14 in GC from TCGA database. There were 3 (cg27485084, cg12053284 and cg16222762), 10 (cg08913010, (cg02269161, cg03226737, cg08185661, cg14243481, cg16437728, cg18560328, cg22723056, cg24678137 and cg26945996) and 8 (cg04932544, cg15389528, cg02795029, cg07581146, cg15149095, cg19922137, cg25371503 and cg26158959) methylation cg sites corresponded to SYT4, SYT9 and SYT14, respectively (Fig. 5A, 5B and 5C). The Pearson's correlation analysis demonstrated the inverse correlation between mRNA expression and methylation levels of SYT4, SYT9 and SYT14 (R=-0.16, P = 0,0025; R=-0.37, P < 0.001 and R=-0.17, P = 0.0016, respectively) (Fig. 5D, 5E and 5F).
Indeed, We found that except for 1 methylation cg site (cg27485084) (P = 0.12) (Fig. 6A), 2 methylation cg sites (cg12053284 and cg16222762) negatively correlated with the expression of SYT4 (P = 0.016 and P = 0.023) (Fig. 6B and 6C). Moreover, we discovered that except for 1 methylation cg site (cg08913010) (P = 0.38) (Fig. 6D), 9 methylation cg sites (cg02269161, cg03226737, cg08185661, cg14243481, cg16437728, cg18560328, cg22723056, cg24678137 and cg26945996) inversely correlated with the expression of SYT9 (all P < 0.001) (Fig. 6E, 6F, 6G, 6H, 6I, 6J, 6K, 6L and 6M). Furthermore, we demonstrated that except for 2 methylation cg sites (cg04932544 and cg15389528) (P = 0.13 and P = 0.051) (Fig. 6N and 6O), 6 methylation cg sites (cg02795029, cg07581146, cg15149095, cg19922137, cg25371503 and cg26158959) were negative association with the expression of SYT14 (all P < 0.001) (Fig. 6P, 6Q, 6R, 6S, 6T and 6U).
Validation the prognostic value of different methylation cg sites in GC
Then, Kaplan-Meier survival analysis was used to investigate the prognostic values of methylation cg sites of SYT4, SYT9 and SYT14 in patients with GC from TCGA database. We found that the methylation cg sites levels (cg27485084, cg12053284 and cg16222762) of SYT4 were not associated with OS (P = 0.108, P = 0.283 and P = 0.145, respectively) (Fig. 7A, 7B and 7C). Moreover, we discovered that the low methylation cg sites levels (cg02269161, cg03226737, cg08185661, cg18560328, cg22723056 and cg24678137) of SYT9 were correlated with unfavorable OS (P = 0.004, P = 0.014, P = 0.037, P = 0.001, P = 0.005 and P = 0.007, respectively) (Fig. 7D, 7E, 7F, 7G, 7H and 7I), whereas others (cg08913010, cg14243481, cg16437728 and cg26945996) did not have prognostic value for patients with GC (P = 0.926, P = 0.065, P = 0.059 and P = 0.056, respectively) (Fig. 7J, 7K, 7L and 7M). Furthermore, we demonstrated that the low methylation cg sites levels (cg07581146, cg15389528 and cg25371503) of SYT14 were associated with unsatisfactory OS (P = 0.026, P = 0.027 and P = 0.031, respectively) (Fig. 7N, 7O and 7P), whereas others (cg02795029, cg04932544, cg15149095, cg19922137 and cg26158959) were not associated with prognostic value for patients with GC (P = 0.160, P = 0.390, P = 0.382, P = 0.346 and P = 0.164) (Fig. 7Q, 7R, 7S, 7T and 7U).
Similarly, we found that the methylation cg sites levels (cg27485084, cg12053284 and cg16222762) of SYT4 were not associated with PFS (P = 0.359, P = 0.828 and P = 0.584, respectively) (Fig. 8A, 8B and 8C). Moreover, we discovered that the low methylation cg sites levels (cg02269161, cg03226737, cg08185661, cg16437728, cg18560328, cg22723056 and cg24678137) of SYT9 were associated with unfavorable PFS (P < 0.001, P = 0.044, P = 0.002, P = 0.015, P = 0.004, P = 0.028 and P = 0.005, respectively) (Fig. 8D, 8E, 8F, 8G, 8H, 8I and 8J), whereas others (cg08913010, cg14243481 and cg26945996) were not associated with prognostic value for patients with GC (P = 0.564, P = 0.075 and P = 0.122, respectively) (Fig. 8K, 8L and 8M). Furthermore, we demonstrated that the low methylation cg sites levels (cg07581146 and cg19922137) of SYT14 were correlated with unfavorable PFS (P = 0.041 and P = 0.010) (Fig. 8N and 8O), whereas others (cg02795029, cg04932544, cg15149095, cg15389528, cg25371503 and cg26158959) were not correlated with prognostic value for patients with GC (P = 0.112, P = 0.139, P = 0.635, P = 0.059, P = 0.205 and P = 0.061, respectively) (Fig. 8P, 8Q, 8R, 8S, 8T and 8U).
Association with mRNA expression and methylation levels and clinicopathologic characteristics
We further explored the detailed association of SYT4, SYT9 and SYT14 expression as well as their methylation levels with clinicopathologic characteristics. As shown in Table 1 and Table 2, the expression of SYT4 was closely correlated with T stage (P = 0.0029) and pathological stage (P = 0.0181), while the methylation levels of SYT4 were closely correlated with T stage (P = 0.0192). As shown in Table 3 and Table 4, the expression of SYT9 was closely associated with T stage (P = 0.0159), meanwhile the methylation levels of SYT9 were closely associated with M stage (P = 0.0032). As shown in Table 5 and Table 6, the expression of SYT14 was closely correlated with T stage (P = 0.0129), meanwhile the methylation levels of SYT14 were closely correlated with age (P = 0.0208) and pathological stage (P = 0.0273).
Table 1
Correlation between SYT4 mRNA expression and clinicopathologic characteristics in TCGA database
|
|
Total
|
High
|
Low
|
P-value
|
Age a
|
<=65
|
155(45.86%)
|
84(49.7%)
|
71(42.01%)
|
0.156
|
Age
|
> 65
|
179(52.96%)
|
82(48.52%)
|
97(57.4%)
|
|
Age
|
unknow
|
4(1.18%)
|
3(1.78%)
|
1(0.59%)
|
|
Gender a
|
female
|
118(34.91%)
|
60(35.5%)
|
58(34.32%)
|
0.9092
|
Gender
|
male
|
220(65.09%)
|
109(64.5%)
|
111(65.68%)
|
|
Grade a
|
G2
|
123(36.39%)
|
46(27.22%)
|
77(45.56%)
|
|
Grade
|
G3
|
198(58.58%)
|
114(67.46%)
|
84(49.7%)
|
|
Grade
|
unknow
|
9(2.66%)
|
5(2.96%)
|
4(2.37%)
|
|
M a
|
M0
|
301(89.05%)
|
148(87.57%)
|
153(90.53%)
|
0.6162
|
M
|
M1
|
19(5.62%)
|
11(6.51%)
|
8(4.73%)
|
|
M
|
unknow
|
18(5.33%)
|
10(5.92%)
|
8(4.73%)
|
|
N a
|
N0
|
103(30.47%)
|
45(26.63%)
|
58(34.32%)
|
0.3329
|
N
|
N1
|
87(25.74%)
|
44(26.04%)
|
43(25.44%)
|
|
N
|
N2
|
71(21.01%)
|
35(20.71%)
|
36(21.3%)
|
|
N
|
N3
|
69(20.41%)
|
40(23.67%)
|
29(17.16%)
|
|
N
|
unknow
|
8(2.37%)
|
5(2.96%)
|
3(1.78%)
|
|
T a
|
T1
|
18(5.33%)
|
3(1.78%)
|
15(8.88%)
|
0.0029
|
T
|
T2
|
67(19.82%)
|
27(15.98%)
|
40(23.67%)
|
|
T
|
T3
|
160(47.34%)
|
84(49.7%)
|
76(44.97%)
|
|
T
|
T4
|
93(27.51%)
|
55(32.54%)
|
38(22.49%)
|
|
Stage a
|
Stage I
|
46(13.61%)
|
13(7.69%)
|
33(19.53%)
|
0.0181
|
Stage
|
Stage II
|
108(31.95%)
|
58(34.32%)
|
50(29.59%)
|
|
Stage
|
Stage III
|
145(42.9%)
|
73(43.2%)
|
72(42.6%)
|
|
Stage
|
Stage IV
|
29(8.58%)
|
17(10.06%)
|
12(7.1%)
|
|
Stage
|
unknow
|
10(2.96%)
|
8(4.73%)
|
2(1.18%)
|
|
Note: a, Chi-squared test |
Table 2
Correlation between SYT4 methylation levels and clinicopathologic characteristics in TCGA database
|
|
Total
|
High
|
Low
|
P-value
|
Age a
|
<=65
|
155(45.86%)
|
70(41.42%)
|
85(50.3%)
|
0.1245
|
Age
|
> 65
|
179(52.96%)
|
97(57.4%)
|
82(48.52%)
|
|
Age
|
unknow
|
4(1.18%)
|
2(1.18%)
|
2(1.18%)
|
|
Gender a
|
female
|
118(34.91%)
|
51(30.18%)
|
67(39.64%)
|
0.087
|
Gender
|
male
|
220(65.09%)
|
118(69.82%)
|
102(60.36%)
|
|
Grade a
|
G1
|
8(2.37%)
|
3(1.78%)
|
5(2.96%)
|
0.2182
|
Grade
|
G2
|
123(36.39%)
|
56(33.14%)
|
67(39.64%)
|
|
Grade
|
G3
|
198(58.58%)
|
108(63.91%)
|
90(53.25%)
|
|
Grade
|
unknow
|
9(2.66%)
|
2(1.18%)
|
7(4.14%)
|
|
M a
|
M0
|
301(89.05%)
|
151(89.35%)
|
150(88.76%)
|
1
|
M
|
M1
|
19(5.62%)
|
10(5.92%)
|
9(5.33%)
|
|
M
|
unknow
|
18(5.33%)
|
8(4.73%)
|
10(5.92%)
|
|
N a
|
N0
|
103(30.47%)
|
52(30.77%)
|
51(30.18%)
|
0.5057
|
N
|
N1
|
87(25.74%)
|
43(25.44%)
|
44(26.04%)
|
|
N
|
N2
|
71(21.01%)
|
40(23.67%)
|
31(18.34%)
|
|
N
|
N3
|
69(20.41%)
|
30(17.75%)
|
39(23.08%)
|
|
N
|
unknow
|
8(2.37%)
|
4(2.37%)
|
4(2.37%)
|
|
T a
|
T1
|
18(5.33%)
|
11(6.51%)
|
7(4.14%)
|
0.0192
|
T
|
T2
|
67(19.82%)
|
28(16.57%)
|
39(23.08%)
|
|
T
|
T3
|
160(47.34%)
|
77(45.56%)
|
83(49.11%)
|
|
T
|
T4
|
93(27.51%)
|
53(31.36%)
|
40(23.67%)
|
|
Stage a
|
Stage I
|
46(13.61%)
|
18(10.65%)
|
28(16.57%)
|
0.2368
|
Stage
|
Stage II
|
108(31.95%)
|
55(32.54%)
|
53(31.36%)
|
|
Stage
|
Stage III
|
145(42.9%)
|
79(46.75%)
|
66(39.05%)
|
|
Stage
|
Stage IV
|
29(8.58%)
|
12(7.1%)
|
17(10.06%)
|
|
Stage
|
unknow
|
10(2.96%)
|
5(2.96%)
|
5(2.96%)
|
|
Note: a, Chi-squared test |
Table 3
Correlation between SYT9 mRNA expression and clinicopathologic characteristics in TCGA database
|
|
Total
|
High
|
Low
|
P-value
|
Age a
|
<=65
|
155(45.86%)
|
88(52.07%)
|
67(39.64%)
|
0.065
|
Age
|
> 65
|
179(52.96%)
|
81(47.93%)
|
98(57.99%)
|
|
Age
|
unknow
|
4(1.18%)
|
0(0%)
|
4(2.37%)
|
|
Gender a
|
female
|
118(34.91%)
|
53(31.36%)
|
65(38.46%)
|
0.2094
|
Gender
|
male
|
220(65.09%)
|
116(68.64%)
|
104(61.54%)
|
|
Grade a
|
G2
|
123(36.39%)
|
48(28.4%)
|
75(44.38%)
|
|
Grade
|
G3
|
198(58.58%)
|
113(66.86%)
|
85(50.3%)
|
|
Grade
|
unknow
|
9(2.66%)
|
4(2.37%)
|
5(2.96%)
|
|
M a
|
M0
|
301(89.05%)
|
144(85.21%)
|
157(92.9%)
|
0.2897
|
M
|
M1
|
19(5.62%)
|
12(7.1%)
|
7(4.14%)
|
|
M
|
unknow
|
18(5.33%)
|
13(7.69%)
|
5(2.96%)
|
|
N a
|
N0
|
103(30.47%)
|
52(30.77%)
|
51(30.18%)
|
0.9095
|
N
|
N1
|
87(25.74%)
|
41(24.26%)
|
46(27.22%)
|
|
N
|
N2
|
71(21.01%)
|
37(21.89%)
|
34(20.12%)
|
|
N
|
N3
|
69(20.41%)
|
36(21.3%)
|
33(19.53%)
|
|
N
|
unknow
|
8(2.37%)
|
3(1.78%)
|
5(2.96%)
|
|
T a
|
T1
|
18(5.33%)
|
6(3.55%)
|
12(7.1%)
|
0.0159
|
T
|
T2
|
67(19.82%)
|
30(17.75%)
|
37(21.89%)
|
|
T
|
T3
|
160(47.34%)
|
79(46.75%)
|
81(47.93%)
|
|
T
|
T4
|
93(27.51%)
|
54(31.95%)
|
39(23.08%)
|
|
Stage a
|
Stage I
|
46(13.61%)
|
21(12.43%)
|
25(14.79%)
|
0.5991
|
Stage
|
Stage II
|
108(31.95%)
|
49(28.99%)
|
59(34.91%)
|
|
Stage
|
Stage III
|
145(42.9%)
|
76(44.97%)
|
69(40.83%)
|
|
Stage
|
Stage IV
|
29(8.58%)
|
16(9.47%)
|
13(7.69%)
|
|
Stage
|
unknow
|
10(2.96%)
|
7(4.14%)
|
3(1.78%)
|
|
Note: a, Chi-squared test |
Table 4
Correlation between SYT9 methylation levels and clinicopathologic characteristics in TCGA database
|
|
Total
|
High
|
Low
|
P-value
|
Age a
|
<=65
|
155(45.86%)
|
66(39.05%)
|
89(52.66%)
|
0.0208
|
Age
|
> 65
|
179(52.96%)
|
100(59.17%)
|
79(46.75%)
|
|
Age
|
unknow
|
4(1.18%)
|
3(1.78%)
|
1(0.59%)
|
|
Gender a
|
female
|
118(34.91%)
|
59(34.91%)
|
59(34.91%)
|
1
|
Gender
|
male
|
220(65.09%)
|
110(65.09%)
|
110(65.09%)
|
|
Grade a
|
G1
|
8(2.37%)
|
5(2.96%)
|
3(1.78%)
|
0.5796
|
Grade
|
G2
|
123(36.39%)
|
66(39.05%)
|
57(33.73%)
|
|
Grade
|
G3
|
198(58.58%)
|
97(57.4%)
|
101(59.76%)
|
|
Grade
|
unknow
|
9(2.66%)
|
1(0.59%)
|
8(4.73%)
|
|
M a
|
M0
|
301(89.05%)
|
161(95.27%)
|
140(82.84%)
|
0.0032
|
M
|
M1
|
19(5.62%)
|
3(1.78%)
|
16(9.47%)
|
|
M
|
unknow
|
18(5.33%)
|
5(2.96%)
|
13(7.69%)
|
|
N a
|
N0
|
103(30.47%)
|
60(35.5%)
|
43(25.44%)
|
0.2003
|
N
|
N1
|
87(25.74%)
|
38(22.49%)
|
49(28.99%)
|
|
N
|
N2
|
71(21.01%)
|
37(21.89%)
|
34(20.12%)
|
|
N
|
N3
|
69(20.41%)
|
32(18.93%)
|
37(21.89%)
|
|
N
|
unknow
|
8(2.37%)
|
2(1.18%)
|
6(3.55%)
|
|
T a
|
T1
|
18(5.33%)
|
11(6.51%)
|
7(4.14%)
|
0.3756
|
T
|
T2
|
67(19.82%)
|
28(16.57%)
|
39(23.08%)
|
|
T
|
T3
|
160(47.34%)
|
84(49.7%)
|
76(44.97%)
|
|
T
|
T4
|
93(27.51%)
|
46(27.22%)
|
47(27.81%)
|
|
Stage a
|
Stage I
|
46(13.61%)
|
22(13.02%)
|
24(14.2%)
|
0.1083
|
Stage
|
Stage II
|
108(31.95%)
|
61(36.09%)
|
47(27.81%)
|
|
Stage
|
Stage III
|
145(42.9%)
|
73(43.2%)
|
72(42.6%)
|
|
Stage
|
Stage IV
|
29(8.58%)
|
9(5.33%)
|
20(11.83%)
|
|
Stage
|
unknow
|
10(2.96%)
|
4(2.37%)
|
6(3.55%)
|
|
Note: a, Chi-squared test |
Table 5
Correlation between SYT14 mRNA expression and clinicopathologic characteristics in TCGA database
|
|
Total
|
High
|
Low
|
P-value
|
Age a
|
<=65
|
155(45.86%)
|
81(47.93%)
|
74(43.79%)
|
0.6493
|
Age
|
> 65
|
179(52.96%)
|
88(52.07%)
|
91(53.85%)
|
|
Age
|
unknow
|
4(1.18%)
|
0(0%)
|
4(2.37%)
|
|
Gender a
|
female
|
118(34.91%)
|
56(33.14%)
|
62(36.69%)
|
0.5683
|
Gender
|
male
|
220(65.09%)
|
113(66.86%)
|
107(63.31%)
|
|
Grade a
|
G1
|
8(2.37%)
|
4(2.37%)
|
4(2.37%)
|
0.4257
|
Grade
|
G2
|
123(36.39%)
|
56(33.14%)
|
67(39.64%)
|
|
Grade
|
G3
|
198(58.58%)
|
105(62.13%)
|
93(55.03%)
|
|
Grade
|
unknow
|
9(2.66%)
|
4(2.37%)
|
5(2.96%)
|
|
M a
|
M0
|
301(89.05%)
|
151(89.35%)
|
150(88.76%)
|
1
|
M
|
M1
|
19(5.62%)
|
9(5.33%)
|
10(5.92%)
|
|
M
|
unknow
|
18(5.33%)
|
9(5.33%)
|
9(5.33%)
|
|
N a
|
N0
|
103(30.47%)
|
52(30.77%)
|
51(30.18%)
|
0.9068
|
N
|
N1
|
87(25.74%)
|
46(27.22%)
|
41(24.26%)
|
|
N
|
N2
|
71(21.01%)
|
34(20.12%)
|
37(21.89%)
|
|
N
|
N3
|
69(20.41%)
|
33(19.53%)
|
36(21.3%)
|
|
N
|
unknow
|
8(2.37%)
|
4(2.37%)
|
4(2.37%)
|
|
T a
|
T1
|
18(5.33%)
|
6(3.55%)
|
12(7.1%)
|
0.0129
|
T
|
T2
|
67(19.82%)
|
26(15.38%)
|
41(24.26%)
|
|
T
|
T3
|
160(47.34%)
|
94(55.62%)
|
66(39.05%)
|
|
T
|
T4
|
93(27.51%)
|
43(25.44%)
|
50(29.59%)
|
|
Stage a
|
Stage I
|
46(13.61%)
|
18(10.65%)
|
28(16.57%)
|
0.2135
|
Stage
|
Stage II
|
108(31.95%)
|
57(33.73%)
|
51(30.18%)
|
|
Stage
|
Stage III
|
145(42.9%)
|
76(44.97%)
|
69(40.83%)
|
|
Stage
|
Stage IV
|
29(8.58%)
|
11(6.51%)
|
18(10.65%)
|
|
Stage
|
unknow
|
10(2.96%)
|
7(4.14%)
|
3(1.78%)
|
|
Note: a, Chi-squared test |
Table 6
Correlation between SYT14 methylation levels and clinicopathologic characteristics in TCGA database
|
|
Total
|
High
|
Low
|
P-value
|
Age a
|
<=65
|
155(45.86%)
|
66(39.05%)
|
89(52.66%)
|
0.0208
|
Age
|
> 65
|
179(52.96%)
|
100(59.17%)
|
79(46.75%)
|
|
Age
|
unknow
|
4(1.18%)
|
3(1.78%)
|
1(0.59%)
|
|
Gender a
|
female
|
118(34.91%)
|
56(33.14%)
|
62(36.69%)
|
0.5683
|
Gender
|
male
|
220(65.09%)
|
113(66.86%)
|
107(63.31%)
|
|
Grade a
|
G1
|
8(2.37%)
|
2(1.18%)
|
6(3.55%)
|
0.3453
|
Grade
|
G2
|
123(36.39%)
|
63(37.28%)
|
60(35.5%)
|
|
Grade
|
G3
|
198(58.58%)
|
101(59.76%)
|
97(57.4%)
|
|
Grade
|
unknow
|
9(2.66%)
|
3(1.78%)
|
6(3.55%)
|
|
M a
|
M0
|
301(89.05%)
|
157(92.9%)
|
144(85.21%)
|
0.0513
|
M
|
M1
|
19(5.62%)
|
5(2.96%)
|
14(8.28%)
|
|
M
|
unknow
|
18(5.33%)
|
7(4.14%)
|
11(6.51%)
|
|
N a
|
N0
|
103(30.47%)
|
60(35.5%)
|
43(25.44%)
|
0.0912
|
N
|
N1
|
87(25.74%)
|
40(23.67%)
|
47(27.81%)
|
|
N
|
N2
|
71(21.01%)
|
39(23.08%)
|
32(18.93%)
|
|
N
|
N3
|
69(20.41%)
|
28(16.57%)
|
41(24.26%)
|
|
N
|
unknow
|
8(2.37%)
|
2(1.18%)
|
6(3.55%)
|
|
T a
|
T1
|
18(5.33%)
|
11(6.51%)
|
7(4.14%)
|
0.5695
|
T
|
T2
|
67(19.82%)
|
31(18.34%)
|
36(21.3%)
|
|
T
|
T3
|
160(47.34%)
|
77(45.56%)
|
83(49.11%)
|
|
T
|
T4
|
93(27.51%)
|
50(29.59%)
|
43(25.44%)
|
|
Stage a
|
Stage I
|
46(13.61%)
|
23(13.61%)
|
23(13.61%)
|
0.0273
|
Stage
|
Stage II
|
108(31.95%)
|
60(35.5%)
|
48(28.4%)
|
|
Stage
|
Stage III
|
145(42.9%)
|
74(43.79%)
|
71(42.01%)
|
|
Stage
|
Stage IV
|
29(8.58%)
|
7(4.14%)
|
22(13.02%)
|
|
Stage
|
unknow
|
10(2.96%)
|
5(2.96%)
|
5(2.96%)
|
|
Note: a, Chi-squared test |
Association of SYTs family members expression with immune cells infiltration
According to increasing evidence on the correlations between immune cells infiltration and prognosis in cancer, we utilized the TIMER database to evaluate the association of SYT4, SYT9 and SYT14 expression with immune cells infiltration. As shown in Fig. 9A, 9B, 9C, 9D and 9E, the expression of SYT4 was positively correlated with CD4+T cells, CD8+T cells, DC, macrophage cells and neutrophil cells (all P < 0.001), whereas which had no correlation with B cells (P = 0.881) (Fig. 9F). As shown in Fig. 9G, 9H, 9I, 9J, 9K and 9L, the expression of SYT9 had positive association with B cells, CD4+T cells, CD8+T cells, DC, macrophage cells and neutrophil cells (all P < 0.001). As shown in Fig. 9M and 9N, the expression of SYT14 was positively associated with CD4+T cells and macrophage cells (all p < 0.001), whereas which was not associated with B cells, CD8+T cells, DC and neutrophil cells (P = 0.52, P = 0.51, P = 0.96 and P = 0.81, respectively) (Fig. 9O, 9P, 9Q and 9R).