Liu YZ, Han DT, Shi DR, Hong B, Qian Y, Wu ZG, Yao SH, Tang TM, Wang MH, Xu XM, Yao HP. Pathological significance of abnormal recepteur d’origine nantais and programmed death ligand 1 expression in colorectal cancer. World J Gastrointest Oncol 2020; 12(11): 1216-1236 [PMID: 33250957 DOI: 10.4251/wjgo.v12.i11.1216]
Corresponding Author of This Article
Hang-Ping Yao, PhD, Professor, Department of Cancer Biology Research, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. yaohangping@zju.edu.cn
Research Domain of This Article
Pathology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Nov 15, 2020; 12(11): 1216-1236 Published online Nov 15, 2020. doi: 10.4251/wjgo.v12.i11.1216
Table 1 Comparison of RON and PD-L1 expression and clinicopathological characteristics of patients with colorectal cancer in the FAHZUSM and Gene Expression Omnibus cohorts, n (%)
Table 2 Comparison of RON (tumor cells) and PD-L1 (tumor cells) expression and clinicopathological characteristics of patients with colorectal cancer in the FAHZUSM cohort, n (%)
Characteristic
Cases
RON and PD-L1 (TCs) expression in the tumor microenvironment
RON low/PD-L1 low
RON high/PD-L1 low
RON low/PD-L1 high
RON high/PD-L1 high
P value
Number of cases
290
177
70
18
25
Age (mean ± SD)
60.89 ± 12.215
60.37 ± 12.299
62.40 ± 12.518
58.39 ± 12.930
62.12 ± 10.179
0.495
Sex
Man
161 (55.5)
108 (61)
35 (50.0)
9 (50.0)
9 (36.0)
0.061
Women
129 (44.5)
68 (39)
35 (50.0)
9 (50.0)
16 (64.0)
Principal diagnosis
s
Rectum
182 (62.8)
116 (65.5)
37 (52.9)
14 (77.8)
15 (60.0)
0.149
Colon
108 (37.2)
61 (34.5)
33 (47.1)
4 (22.2)
10 (40.0)
Pathological grade
Well/moderate
6 (2.1)
3 (1.7)
2 (2.9)
0 (0.0)
1 (4.0)
0.264
Poor
264 (9.1)
158 (89.3)
66 (94.3)
16 (88.9)
24 (96.0)
Unknown
20 (6.9)
16 (9.0)
2 (2.9)
2 (11.1)
0 (0.0)
T stage
Tis-T2
84 (29)
64 (36.2)
9 (12.9)
5 (27.8)
6 (24.0)
0.003
T3
140 (48.3)
82 (46.3)
36 (51.4)
11 (61.1)
11 (44.0)
T4
66 (22.8)
31 (17.5)
25 (35.7)
2 (11.1)
8 (32.0)
N stage
N0
238 (66.9)
125 (70.6)
39 (55.7)
12 (66.7)
13 (66.4)
0.072
N (1-2)
118 (33.1)
52 (29.4)
31 (44.3)
6 (33.3)
12 (33.6)
M stage
M0
283 (97.6)
173 (97.7)
68 (97.1)
18 (100)
24 (96.0)
0.735
M1
7 (2.4)
4 (2.3)
2 (2.9)
0 (0.0)
1 (4.0)
Stage
0-II
187 (64.5)
123 (69.5)
39 (55.7)
12 (66.7)
13 (52.0)
0.110
III-IV
103 (35.5)
54 (30.5)
31 (33.3)
6 (33.3)
12 (48.0)
Histological type
Adenocarcinoma
251 (86.6)
152 (85.9)
62 (88.6)
15 (83.3)
22 (88.0)
0.493
Mucinous/SRCC
32 (11)
21 (11.9)
7 (10.0)
1 (5.6)
3 (12.0)
Other
7 (2.4)
4 (2.3)
1 (1.4)
2 (11.1)
0 (0.0)
Treatment
Yes
135 (46.6)
83 (46.9)
22 (31.4)
6 (33.3)
12 (48.0)
0.158
No
119 (41.0)
74 (41.8)
38 (54.3)
11 (61.1)
8 (32.0)
Unknown
36 (12.4)
20 (11.3)
10 (14.3)
1 (5.6)
5 (20.0)
Table 3 Comparison of RON (tumor cells) and PD-L1 (tumor-infiltrating mononuclear cells) expression and clinicopathological characteristics of patients with colorectal cancer in the FAHZUSM cohort, n (%)
Characteristic
Cases
RON and PD-L1 (TIMCs) expression in the tumor microenvironment
RON low/PD-L1 low
RON high/PD-L1 low
RON low/PD-L1 high
RON high/PD-L1 high
P value
Number of cases
338
177
70
65
26
Age (mean ± SD)
61.24 ± 12.555
60.37 ± 12.299
62.40 ± 12.518
61.03 ± 13.286
64.58 ± 12.436
0.348
Sex
Man
197 (58.3)
108 (61)
35 (50.0)
40 (61.5)
14 (52.8)
0.368
Women
141 (41.7)
68 (39)
35 (50.0)
25 (38.5)
12 (46.2)
Principal diagnosis
Rectum
200 (59.2)
116 (65.5)
37 (52.9)
28 (43.1)
19 (73.1)
0.004
Colon
138 (40.8)
61 (34.5)
33 (47.1)
37 (56.9)
7 (26.9)
Pathological grade
Well/moderate
8 (2.4)
3 (1.7)
2 (2.9)
3 (4.6)
0 (0)
0.492
Poor
306 (90.5)
158 (89.3)
66 (94.3)
58 (89.2)
24 (92.3)
Unknown
24 (7.1)
16 (9.0)
2 (2.9)
4 (6.2)
2 (7.7)
T stage
Tis-T2
96 (28.4)
64 (36.2)
9 (12.9)
16 (2.6)
7 (26.9)
0.002
T3
155 (45.9)
82 (46.3)
36 (51.4)
28 (43.1)
9 (34.6)
T4
87 (25.7)
31 (17.5)
25 (35.7)
21 (32.3)
10 (38.5)
N stage
N0
226 (66.9)
125 (70.6)
39 (55.7)
47 (72.3)
15 (57.7)
0.075
N (1-2)
112 (33.1)
52 (29.4)
31 (44.3)
18 (27.7)
11 (42.3)
M stage
M0
326 (96.4)
173 (97.7)
68 (97.1)
61 (93.8)
24 (92.3)
0.235
M1
12 (3.6)
4 (2.3)
2 (2.9)
4 (2.3)
2 (7.7)
Stage
0-II
221 (65.4)
123 (69.5)
39 (55.7)
45 (69.2)
14 (53.8)
0.104
III-IV
117 (34.6)
54 (30.5)
31 (33.3)
20 (30.8)
12 (46.2)
Histological type
Adenocarcinoma
287 (84.9)
152 (85.9)
62 (88.6)
60 (92.3)
13 (50)
< 0.001
Mucinous/SRCC
40 (11.8)
21 (11.9)
7 (10.0)
3 (4.6)
9 (34.6)
Other
11 (3.3)
4 (2.3)
1 (1.4)
2 (3.1)
4 (15.4)
Treatment
Yes
298 (88.2)
83 (46.9)
22 (31.4)
30 (46.2)
24 (92.3)
< 0.001
No
32 (9.5)
74 (41.8)
38 (54.3)
25 (38.5)
1 (3.8)
Unknown
8 (2.4)
20 (11.3)
10 (14.3)
10 (15.4)
1 (3.8)
Table 4 Univariate and multivariate Cox proportional hazard analyses of overall survival in patients with colorectal cancer in the FAHZUSM and Gene Expression Omnibus cohorts
Variable
FAHZUSM cohort
GEO cohort
Univariate analysis, HR (95%CI)
P value
Multivariate analysis, HR (95%CI)
P value
Univariate analysis, HR (95%CI)
P value
Multivariate analysis, HR (95%CI)
P value
Age (mean ± SD)
1.029 (1.011-1.048)
0.002
1.031 (1.011-1.050)
0.002
1.025 (1.009-1.041)
0.002
1.028 (1.012-1.045)
0.001
Gender
Male
1.000
0.011
1.000
0.008
1.000
0.293
1.000
0.076
Female
0.562 (0.362-0.874)
0.527 (0.328-0.847)
0.814 (0.555-1.194)
0.698 (0.469-1.039)
Principal diagnosis
Rectum
1.000
0.298
1.000
0.318
1.000
0.688
1.000
0.544
Colon
0.796 (0.518-1.224)
0.790 (0.497-1.255)
1.081 (0.738-1.585)
0.882 (0.589-1.322)
Histological type
Adenocarcinoma
1.000
0.408
1.000
0.387
NA
Mucinous/SRCC
2.464 (0.343-17.710)
2.720 (0.263-28.122)
Unknown
3.355 (0.433-25.986)
1.232 (0.129-11.795)
T stage
Tis-T2
1.000
< 0.001
1.000
0.003
1.000
0.001
1.000
0.007
T3
0.211 (0.108-0.413)
0.298 (0.141-0.632)
0.333 (0.145-0.766)
0.381 (0.159-0.914)
T4
0.503 (0.325-0.781)
0.596 (0.361-0.897)
0.455 (0.292-0.709)
0.476 (0.295-0.769)
N stage
N0
1.000
< 0.001
1.000
0.111
1.000
0.062
1.000
0.141
N (1-2)
3.156 (2.083-4.783)
5.376 (0.678-42.660)
1.435 (0.982-2.097)
0.306 (0.063-1.479)
M stage
M0
1.000
< 0.001
1.000
0.039
1.000
< 0.001
1.000
0.008
M1
4.338 (2.094-8.985)
2.445 (1.048-5.701)
3.546 (2.013-6.247)
2.481 (1.269-4.852)
Stage
0-II
1.000
< 0.001
1.000
0.406
1.000
0.029
1.000
0.099
III-IV
3.102 (2.044-4.708)
0.409 (0.050-3.366)
1.530 (1.045-2.242)
3.924 (0.774-19.888)
Pathological grade
Well/moderate
1.000
< 0.001
1.000
0.003
NA
Poor
7.689 (2.434-24.290)
4.044 (1.103-14.830)
Unknown
1.266 (0.513-3.126)
0.375 (0.104-1.357)
RON (protein)
Low
1.000
0.001
1.000
0.012
1.000
0.035
1.000
0.466
High
2.060 (1.364-3.112)
1.788 (1.138-2.808)
1.515 (1.030-2.228)
1.170 (0.767-1.785)
RON (mRNA)
Low
NA
1.000
0.035
1.000
0.466
High
1.515 (1.030-2.228)
1.170 (0.767-1.785)
PD-L1 (protein)
Low
1.000
< 0.001
1.000
0.001
NA
High (TIMCs)
0.544 (0.293-1.011)
0.676 (0.350-1.304)
High (TCs)
1.325 (0.669-2.511)
1.654 (0.819-3.338)
PD-L1 (mRNA)
Low
NA
1.000
0.047
1.000
0.083
High
1.835 (1.007-3.345)
1.719 (0.931-3.173)
Citation: Liu YZ, Han DT, Shi DR, Hong B, Qian Y, Wu ZG, Yao SH, Tang TM, Wang MH, Xu XM, Yao HP. Pathological significance of abnormal recepteur d’origine nantais and programmed death ligand 1 expression in colorectal cancer. World J Gastrointest Oncol 2020; 12(11): 1216-1236