Basic Study
Copyright ©The Author(s) 2020.
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 (%)
FAHZUSM cohort (n = 381)
GEO cohort (n = 287)
CharacteristicCasesRON expression
PD-L1 expression
Cases No (%)RON expression
PD-L1 expression
Low
High
1P value
Low
High (TIMC)
2P value
Low
High (TC)
3P value
Low
High
1P value
Low
High (TC)
3P value
No. of cases number38126012124791247432871939448239
Age (mean ± SD)61.16 ± 12.41960.40 ± 12.56062.81 ± 11.9970.85960.94 ± 12.3762.04 ± 13.0800.77160.94 ± 12.3761.16 ± 12.4190.93868.44 ± 14.0066.87 ± 13.1871.65 ± 15.120.00666.94 ± 14.3368.74 ± 13.950.417
Sex
Man215 (56.4)157 (60.4)58 (47.9)0.023143 (57.9)54 (59.3)0.811143 (57.9)18 (41.9)0.051158 (55.1)111 (57.5)47 (50)0.23030 (62.5)128 (53.6)0.256
Women166 (43.6)103 (39.6)63 (52.1)104 (42.1)37 (40.7)104 (42.1)25 (58.1)129 (44.9)82 (42.5)47 (50)18 (37.5)111 (46.4)
Principal diagnosis
Rectum229 (60.1)158 (61.1)71 (58.7)0.698153 (61.9)47 (51.6)0.088153 (61.9)29 (67.4)0.491165 (57.5)111 (57.5)54 (57.4)0.92034 (70.8)131 (54.8)0.040
Colon152 (39.9)102 (38.9)50 (41.3)94 (38.1)44 (48.4)94 (38.1)14 (32.6)122 (42.5)82 (42.5)40 (42.6)14 (29.2)108 (45.2)
Pathological grade
Well/moderate9 (2.4)6 (2.3)3 (2.5)0.1775 (2)3 (3.3)0.7785 (2)1 (2.3)0.898NA
Poor346 (90.8)232 (89.2)114 (94.2)224 (90.7)82 (90.1)224 (90.7)40 (93)
Unknown26 (6.8)22 (8.5)4 (3.3)18 (7.1)6 (6.3)18 (7.3)2 (4.7)
T stage
Tis-T2107 (28.1)85 (32.7)22 (18.2)0.00173 (29.6)23 (25.3)0.10573 (29.6)11 (25.6)0.86428 (9.7)18 (9.3)10 (10.6)0.4593 (6.3)25 (10.5)0.437
T3177 (46.5)121 (46.5)56 (46.3)118 (47.8) (46.8%)37 (40.7)118 (47.8)22 (51.2)208 (72.5)144 (74.6)64 (68.1)2039 (81.3)169 (70.7)
T497 (25.5)54 (20.8)43 (35.5)56 (22.7)31 (34.1)56 (22.7)10 (23.3)51 (17.8)31 (16.1)20 (21.3)6 (12.5)45 (18.8)
N stage
N0251 (65.9)184 (70.8)67 (55.4)0.003164 (66.4)62 (68.1)0.764164 (66.4)25 (58.1)0.294141 (49.1)97 (50.3)44 (46.8)0.58327 (56.3)114 (44.7)0.279
N (1-2)91 (23.9)76 (29.2)54 (44.6)83 (33.6)29 (31.9)83 (33.6)12 (27.9)146 (50.9)96 (49.7)50 (53.2)21 (43.7)125 (52.3)
M stage
M0368 (96.6)252 (96.9)116 (95.9) (96.3%)0.822241 (97.6)85 (93.4)0.133241 (97.6)42 (97.7)1.000268 (93.4)183 (94.8)85 (90.4)0.16047 (97.9)221 (92.5)0.216
M113 (3.4)8 (3.1)5 (4.1)6 (2.4)6 (6.6)6 (2.4)1 (2.3)19 (6.6)10 (5.2)9 (9.6)1 (2.1)18 (7.5)
Disease stage
0-II246 (64.6)180 (69.2)66 (54.5)0.016162 (65.6)59 (64.8)0.897162 (65.6)25 (58.1)0.346139 (48.4)95 (49.2)44 (46.8)0.70127 (56.3)112 (46.9)0.235
III-IV135 (35.4)80 (30.8)55 (45.5)85 (34.4)32 (35.2)85 (34.4)18 (41.9)148 (51.6)98 (50.8)50 (53.2)21 (43.8)127 (53.1)
Histological type
Adenocarcinoma335 (87.9)227 (87.3)108 (89.3)0.706214 (86.6)84 (92.3)0.130214 (86.6)37 (86)0.488287 (100)193 (100)94 (100)48 (100)239 (100)
Mucinous/SRCC36 (9.4)25 (9.6)11 (9.1)28 (11.3)4 (4.4)28 (11.3)4 (9.3)0 (0)0 (0)0 (0)0 (0)0 (0)
Other10 (2.6)8 (3.1)2 (1.7)5 (2.0)3 (3.3)5 (2.0)2 (4.7)0 (0)0 (0)0 (0)0 (0)0 (0)
Treatment
Yes173 (45.4)110 (42.3)63 (52.1)0.043112 (45.3)38 (41.8)0.694112 (45.3)23 (32.6)0.472115 (40.1)89 (46.1)26 (27.7)0.00322 (45.8)93 (38.9)0.372
No158 (41.5)119 (45.8)39 (32.2)105 (42.5)39 (42.9)105 (42.5)14 (53.5)172 (59.9)104 (53.9)68 (72.3)26 (54.2)146 (61.1)
Unknown50 (13.1)31 (11.9)19 (15.7)30 (12.1)14 (15.4)30 (12.1)6 (14)0 (0)0 (0)
PD-L1 (protein)
Low247 (64.8)177 (73.1)70 (26.9)0.9764NA
High (TIMCs)91 (23.9)65 (26.9)26 (27.1)
High (TCs)43 (11.3)18 (9.2)25 (26.3)< 0.0015
PD-L1 (mRNA)
LowNA48 (16.7)31 (16.1)17 (18.1)0.666
High239 (83.3)162 (83.9)77 (81.9)
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 (%)
CharacteristicCasesRON 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 290177701825
Age (mean ± SD)60.89 ± 12.21560.37 ± 12.29962.40 ± 12.51858.39 ± 12.93062.12 ± 10.1790.495
Sex
Man161 (55.5)108 (61)35 (50.0)9 (50.0)9 (36.0)0.061
Women129 (44.5)68 (39)35 (50.0)9 (50.0)16 (64.0)
Principal diagnosiss
Rectum182 (62.8)116 (65.5)37 (52.9)14 (77.8)15 (60.0)0.149
Colon108 (37.2)61 (34.5)33 (47.1)4 (22.2)10 (40.0)
Pathological grade
Well/moderate6 (2.1)3 (1.7)2 (2.9)0 (0.0)1 (4.0)0.264
Poor264 (9.1)158 (89.3)66 (94.3)16 (88.9)24 (96.0)
Unknown20 (6.9)16 (9.0)2 (2.9)2 (11.1)0 (0.0)
T stage
Tis-T284 (29)64 (36.2)9 (12.9)5 (27.8)6 (24.0)0.003
T3140 (48.3)82 (46.3)36 (51.4)11 (61.1)11 (44.0)
T466 (22.8)31 (17.5)25 (35.7)2 (11.1)8 (32.0)
N stage
N0238 (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
M0283 (97.6)173 (97.7)68 (97.1)18 (100)24 (96.0)0.735
M17 (2.4)4 (2.3)2 (2.9)0 (0.0)1 (4.0)
Stage
0-II187 (64.5)123 (69.5)39 (55.7)12 (66.7)13 (52.0)0.110
III-IV103 (35.5)54 (30.5)31 (33.3)6 (33.3)12 (48.0)
Histological type
Adenocarcinoma251 (86.6)152 (85.9)62 (88.6)15 (83.3)22 (88.0)0.493
Mucinous/SRCC32 (11)21 (11.9)7 (10.0)1 (5.6)3 (12.0)
Other7 (2.4)4 (2.3)1 (1.4)2 (11.1)0 (0.0)
Treatment
Yes135 (46.6)83 (46.9)22 (31.4)6 (33.3)12 (48.0)0.158
No119 (41.0)74 (41.8)38 (54.3)11 (61.1)8 (32.0)
Unknown36 (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 (%)
CharacteristicCasesRON 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 cases338177706526
Age (mean ± SD)61.24 ± 12.55560.37 ± 12.29962.40 ± 12.51861.03 ± 13.28664.58 ± 12.4360.348
Sex
Man197 (58.3)108 (61)35 (50.0)40 (61.5)14 (52.8)0.368
Women141 (41.7)68 (39)35 (50.0)25 (38.5)12 (46.2)
Principal diagnosis
Rectum200 (59.2)116 (65.5)37 (52.9)28 (43.1)19 (73.1)0.004
Colon138 (40.8)61 (34.5)33 (47.1)37 (56.9)7 (26.9)
Pathological grade
Well/moderate8 (2.4)3 (1.7)2 (2.9)3 (4.6)0 (0)0.492
Poor306 (90.5)158 (89.3)66 (94.3)58 (89.2)24 (92.3)
Unknown24 (7.1)16 (9.0)2 (2.9)4 (6.2)2 (7.7)
T stage
Tis-T296 (28.4)64 (36.2)9 (12.9)16 (2.6)7 (26.9)0.002
T3155 (45.9)82 (46.3)36 (51.4)28 (43.1)9 (34.6)
T487 (25.7)31 (17.5)25 (35.7)21 (32.3)10 (38.5)
N stage
N0226 (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
M0326 (96.4)173 (97.7)68 (97.1)61 (93.8)24 (92.3)0.235
M112 (3.6)4 (2.3)2 (2.9)4 (2.3)2 (7.7)
Stage
0-II221 (65.4)123 (69.5)39 (55.7)45 (69.2)14 (53.8)0.104
III-IV117 (34.6)54 (30.5)31 (33.3)20 (30.8)12 (46.2)
Histological type
Adenocarcinoma287 (84.9)152 (85.9)62 (88.6)60 (92.3)13 (50)< 0.001
Mucinous/SRCC40 (11.8)21 (11.9)7 (10.0)3 (4.6)9 (34.6)
Other11 (3.3)4 (2.3)1 (1.4)2 (3.1)4 (15.4)
Treatment
Yes298 (88.2)83 (46.9)22 (31.4)30 (46.2)24 (92.3)< 0.001
No32 (9.5)74 (41.8)38 (54.3)25 (38.5)1 (3.8)
Unknown8 (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
VariableFAHZUSM cohort
GEO cohort
Univariate analysis, HR (95%CI)P valueMultivariate analysis, HR (95%CI)P valueUnivariate analysis, HR (95%CI)P valueMultivariate analysis, HR (95%CI)P value
Age (mean ± SD)1.029 (1.011-1.048)0.0021.031 (1.011-1.050)0.0021.025 (1.009-1.041)0.0021.028 (1.012-1.045)0.001
Gender
Male1.0000.0111.0000.0081.0000.2931.0000.076
Female0.562 (0.362-0.874)0.527 (0.328-0.847)0.814 (0.555-1.194)0.698 (0.469-1.039)
Principal diagnosis
Rectum1.0000.2981.0000.3181.0000.6881.0000.544
Colon0.796 (0.518-1.224)0.790 (0.497-1.255)1.081 (0.738-1.585)0.882 (0.589-1.322)
Histological type
Adenocarcinoma1.0000.4081.0000.387NA
Mucinous/SRCC2.464 (0.343-17.710)2.720 (0.263-28.122)
Unknown3.355 (0.433-25.986)1.232 (0.129-11.795)
T stage
Tis-T21.000< 0.0011.0000.0031.0000.0011.0000.007
T30.211 (0.108-0.413)0.298 (0.141-0.632)0.333 (0.145-0.766)0.381 (0.159-0.914)
T40.503 (0.325-0.781)0.596 (0.361-0.897)0.455 (0.292-0.709)0.476 (0.295-0.769)
N stage
N01.000< 0.0011.0000.1111.0000.0621.0000.141
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
M01.000< 0.0011.0000.0391.000< 0.0011.0000.008
M14.338 (2.094-8.985)2.445 (1.048-5.701)3.546 (2.013-6.247)2.481 (1.269-4.852)
Stage
0-II1.000< 0.0011.0000.4061.0000.0291.0000.099
III-IV3.102 (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/moderate1.000< 0.0011.0000.003NA
Poor7.689 (2.434-24.290)4.044 (1.103-14.830)
Unknown1.266 (0.513-3.126)0.375 (0.104-1.357)
RON (protein)
Low1.0000.0011.0000.0121.0000.0351.0000.466
High2.060 (1.364-3.112)1.788 (1.138-2.808)1.515 (1.030-2.228)1.170 (0.767-1.785)
RON (mRNA)
LowNA1.0000.0351.0000.466
High1.515 (1.030-2.228)1.170 (0.767-1.785)
PD-L1 (protein)
Low1.000< 0.0011.0000.001NA
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)
LowNA1.0000.0471.0000.083
High1.835 (1.007-3.345)1.719 (0.931-3.173)