Fig. 1Immunohistochemical expression of silent mating type information regulation 2 homolog 1 (SIRT1), deleted in breast cancer 1 (DBC1), β-catenin, survivin, and p53 in normal colorectal mucosa and colorectal cancer. Normal colorectal mucosa shows SIRT1 expression with weak nuclear staining. DBC1 and survivin are expressed in all of the normal mucosa with moderate to strong intensity. β-catenin shows membranous staining pattern in normal colorectal mucosa. p53 is not expressed in normal mucosa (left panel). Representative figures of positive and negative expression of SIRT, DBC1, β-catenin, survivin, and p53 in adenocarcinoma are shown (middle and right panel, respectively).
Table 1.Clinicopathologic variables and the expression status of SIRT1, DBC1, β-catenin, survivin, and p53
Characteristic |
No. of patients |
SIRT1
|
DBC1
|
β-catenin
|
Survivin
|
p53
|
Positive |
p-value |
Positive |
p-value |
Altered |
p-value |
Positive |
p-value |
Positive |
p-value |
Total |
349 |
235 (67) |
|
183 (52) |
|
246 (70) |
|
193 (55) |
|
190 (54) |
|
Age (yr) |
|
|
|
|
|
|
|
|
|
|
|
< 65 |
186 |
129 (69) |
0.42 |
92 (49) |
0.240 |
131 (70) |
1.00 |
96 (52) |
0.161 |
109 (59) |
0.10 |
≥ 65 |
163 |
106 (65) |
|
91 (56) |
|
115 (71) |
|
97 (60) |
|
81 (50) |
|
Sex |
|
|
|
|
|
|
|
|
|
|
|
Female |
141 |
91 (65) |
0.41 |
68 (48) |
0.230 |
91 (65) |
0.05 |
88 (62) |
0.029 |
68 (48) |
0.06 |
Male |
208 |
144 (69) |
|
115 (55) |
|
155 (75) |
|
105 (50) |
|
122 (59) |
|
Location |
|
|
|
|
|
|
|
|
|
|
|
Right |
76 |
52 (68) |
0.89 |
43 (57) |
0.438 |
41 (54) |
0.001 |
34 (45) |
0.038 |
25 (33) |
< 0.001 |
Left |
273 |
183 (67) |
|
140 (51) |
|
205 (75) |
|
159 (58) |
|
165 (60) |
|
TNM stage |
|
|
|
|
|
|
|
|
|
|
|
I and II |
188 |
130 (69) |
0.49 |
98 (52) |
0.915 |
138 (73) |
0.23 |
103 (55) |
0.914 |
91 (48) |
0.018 |
III and IV |
161 |
105 (65) |
|
85 (53) |
|
108 (67) |
|
90 (56) |
|
99 (61) |
|
Tumor invasion |
|
|
|
|
|
|
|
|
|
|
|
pT1-2 |
77 |
51 (66) |
0.89 |
42 (55) |
0.700 |
53 (69) |
0.77 |
54 (70) |
0.004 |
43 (56) |
0.79 |
pT3-4 |
272 |
184 (68) |
|
141 (52) |
|
193 (71) |
|
139 (51) |
|
147 (54) |
|
LN metastasis |
|
|
|
|
|
|
|
|
|
|
|
Absence |
204 |
137 (67) |
1.00 |
106 (52) |
0.913 |
149 (73) |
0.23 |
108 (53) |
0.326 |
104 (51) |
0.12 |
Presence |
145 |
98 (68) |
|
77 (53) |
|
97 (67) |
|
85 (59) |
|
86 (59) |
|
Distant metastasis |
|
|
|
|
|
|
|
|
|
|
|
Absence |
309 |
212 (69) |
0.20 |
165 (53) |
0.401 |
224 (72) |
0.027 |
175 (57) |
0.179 |
158 (51) |
0.001 |
Presence |
40 |
23 (58) |
|
18 (45) |
|
22 (55) |
|
18 (45) |
|
32 (80) |
|
Histologic grade |
|
|
|
|
|
|
|
|
|
|
|
WD or MD |
342 |
228 (67) |
0.10 |
178 (52) |
0.452 |
244 (71) |
0.026 |
188 (55) |
0.467 |
186 (54) |
1.00 |
PD |
7 |
7 (100) |
|
5 (71) |
|
2 (29) |
|
5 (71) |
|
4 (57) |
|
Table 2.The expression status and correlations of SIRT1, DBC1, β-catenin, survivin, and p53
Characteristic |
No. of patients |
SIRT1
|
DBC1
|
β-catenin
|
Survivin
|
p53
|
Positive |
p-value |
Positive |
p-value |
Altered |
p-value |
Positive |
p-value |
Positive |
p-value |
Total |
349 |
235 (67) |
- |
183 (52) |
- |
246 (70) |
- |
193 (55) |
- |
190 (54) |
- |
SIRT1 |
|
|
|
|
|
|
|
|
|
|
|
Positive |
235 |
- |
- |
144 (61) |
< 0.001 |
179 (76) |
0.001 |
144 (61) |
0.002 |
132 (56) |
0.36 |
Negative |
114 |
- |
|
39 (34) |
|
67 (59) |
|
49 (43) |
|
58 (51) |
|
DBC1 |
|
|
|
|
|
|
|
|
|
|
|
Positive |
183 |
144 (79) |
< 0.001 |
- |
- |
137 (75) |
0.06 |
121 (66) |
< 0.001 |
97 (53) |
0.59 |
Negative |
166 |
91 (55) |
|
- |
|
109 (66) |
|
72 (43) |
|
93 (80) |
|
β-catenin |
|
|
|
|
|
|
|
|
|
|
|
Altered |
246 |
179 (73) |
0.001 |
137 (56) |
0.062 |
- |
- |
144 (59) |
0.07 |
137 (68) |
0.48 |
Non-altered |
103 |
56 (54) |
|
46 (45) |
|
- |
|
49 (48) |
|
53 (51) |
|
Survivin |
|
|
|
|
|
|
|
|
|
|
|
Positive |
193 |
144 (75) |
0.002 |
121 (63) |
< 0.001 |
144 (75) |
0.07 |
- |
- |
98 (51) |
0.13 |
Negative |
156 |
91 (58) |
|
62 (40) |
|
102 (65) |
|
- |
|
92 (59) |
|
p53 |
|
|
|
|
|
|
|
|
|
|
|
Positive |
190 |
132 (69) |
0.36 |
97 (51) |
0.592 |
137 (72) |
0.48 |
98 (52) |
0.13 |
- |
- |
Negative |
159 |
103 (65) |
|
86 (54) |
|
109 (69) |
|
95 (60) |
|
- |
|
Table 3.Clinicopathologic characteristics and their overall survival by univariate Cox proportional hazards regression analysis
Characteristic |
No. of patients |
Overall survival
|
HR (95% CI) |
p-value |
Age (yr) |
|
|
|
< 65 |
186 |
1 |
0.005 |
≥ 65 |
163 |
2.175 (1.269-3.729) |
|
Sex |
|
|
|
Female |
141 |
1 |
0.10 |
Male |
208 |
1.545 (0.919-2.598) |
|
Location |
|
|
|
Right |
76 |
1 |
0.034 |
Left |
273 |
0.546 (0.312-0.955) |
|
TNM stage |
|
|
|
I and II |
188 |
1 |
< 0.001 |
III and IV |
161 |
3.199 (1.812-5.647) |
|
Tumor invasion |
|
|
|
pT1-2 |
77 |
1 |
0.024 |
pT3-4 |
272 |
2.876 (1.149-7.203) |
|
LN metastasis |
|
|
|
Absence |
204 |
1 |
0.001 |
Presence |
145 |
2.392 (1.408-4.064) |
|
Distant metastasis |
|
|
|
Absence |
309 |
1 |
< 0.001 |
Presence |
40 |
7.574 (4.423-12.967) |
|
Histologic grade |
|
|
|
WD or MD |
342 |
1 |
0.001 |
PD |
7 |
5.416 (1.958-14.981) |
|
SIRT1 |
|
|
|
Negative |
114 |
1 |
0.029 |
Positive |
235 |
0.559 (0.332-0.944) |
|
DBC1 |
|
|
|
Negative |
166 |
1 |
0.22 |
Positive |
183 |
1.396 (0.818-2.381) |
|
β-catenin |
|
|
|
Non-altered |
103 |
1 |
0.008 |
Altered |
246 |
0.493 (0.293-0.831) |
|
Survivin |
|
|
|
Negative |
156 |
1 |
0.53 |
Positive |
193 |
1.181 (0.696-2.005) |
|
p53 |
|
|
|
Negative |
159 |
1 |
0.21 |
Positive |
190 |
1.398 (0.820-2.283) |
|
Table 4.Multivariate analysis for overall survival by Cox proportional hazards regression analysis
Characteristic |
No. of patients |
Overall survival
|
HR (95% CI) |
p-value |
Age (yr) |
|
|
|
< 65 |
186 |
1 |
0.001 |
≥ 65 |
163 |
2.563 (1.464-4.486) |
|
Location |
|
|
|
Right |
76 |
1 |
0.15 |
Left |
273 |
0.654 (0.362-1.180) |
|
TNM stage |
|
|
|
I and II |
188 |
1 |
< 0.001 |
III and IV |
161 |
3.501 (1.970-6.220) |
|
Histologic grade |
|
|
|
WD or MD |
342 |
1 |
0.002 |
PD |
7 |
6.350 (2.021-19.952) |
|
SIRT1 |
|
|
|
Negative |
114 |
1 |
0.031 |
Positive |
235 |
0.540 (0.308-0.947) |
|
β-catenin |
|
|
|
Non-altered |
103 |
1 |
0.18 |
Altered |
246 |
0.685 (0.392-1.198) |
|