Elevated RBP-Jκ and CXCL11 Expression in Colon Cancer is Associated with an Unfavorable Clinical Outcome

Figures & data

Table 1 Association of RBP-Jκ and CXCL11 Protein Expression with Clinicopathological Features in 342 Colon Cancer Patients

Characteristics	n	RBP-Jκ			CXCL11
		High	Low	P-value	High	Low	P-value
Histology Type
Tumor tissue (adenocarcinoma)	342	224(65.50%)	118(34.50%)	<0.001	255(74.56%)	87(23.44%)	<0.001
Para-tumor tissue	342	75(21.93%)	267(78.07%)		104(30.41%)	238(69.59%)
Gender
Male	156	97(62.18%)	59(37.82%)	0.237	112(71.79%)	44(28.21%)	0.282
Female	186	127(68.28%)	59(31.72%)		143(76.88%)	43(23.12%)
Age
≤60	111	65(58.56%)	46(41.44%)	0.061	76(68.47%)	35(31.53%)	0.073
>60	231	159(68.83%)	72(31.17%)		179(77.49%)	52(22.51%)
Tumor location
Right colon	288	187(64.93%)	101(35.07%)	0.611	210(72.92%)	78(27.08%)	0.107
Left colon	54	37(68.52%)	17(31.48%)		45(83.33%)	9(16.67%)
Differentiation
Well/Moderate	128	72(56.25%)	56(43.75%)	0.005	86(67.19%)	42(32.81%)	0.015
Poor	214	152(71.03%)	62(28.97%)		169(78.97%)	45(21.03%)
Depth of invasion
Tis/T1/T2	47	24(51.06%)	23(48.94%)	0.025	29(61.70%)	18(38.30%)	0.029
T3/T4	295	200(67.80%)	95(32.20%)		226(76.61%)	69(23.39%)
Lymph node metastasis
No	106	58(54.72%)	48(45.28%)	0.005	71(66.98%)	35(33.02%)	0.031
Yes	236	166(70.34%)	70(29.66%)		184(77.97%)	52(22.03%)
Distant metastasis
No	297	183(61.62%)	114(38.38%)	<0.001	216(72.73%)	81(27.27%)	0.045
Yes	45	41(91.11%)	4(8.89%)		39(86.67%)	6(13.33%)
TNM Stage
I/II	105	57(54.29%)	48(45.71%)	0.004	70(66.67%)	35(33.33%)	0.026
III/IV	237	167(70.46%)	70(29.54%)		185(78.06%)	52(21.94%)

Note: Bold values are statistically significant.

Table 2 Primer Sequences for RT-PCR

Genes	Forward Primer	Reverse Primer
RBP-Jκ	5ʹ-CAAGAGTCTCAACCGTGTGCATTTA-3’	5ʹ-ACATGAAGTGCTTTCGCTTGTCTG-3’
CXCL11	5′-ATAGCCTTGGCTGTGATATTGTGTG-3′	5′-CCTATGCAAAGACAGCGTCCTC-3′
GAPDH	5ʹ-ATGATTCTACCCACGGCAAG-3’	5ʹ-CTGGAAGATGGTGATGGGTT-3’

Table 3 Association of RBP-Jκ and CXCL11 mRNA Expression with Clinicopathological Features in 342 Colon Cancer Patients

Characteristics	n	RBP-Jκ (Mean±SD)	P-value	CXCL11 (Mean±SD)	P-value
Histology Type
Tumor tissue	342	4.04±1.70	<0.001	4.44±2.27	<0.001
Para-tumor tissue	342	1.02±0.41		1.47±0.32
Gender
Male	156	4.03±1.67	0.887	4.65±2.37	0.103
Female	186	4.05±1.72		4.25±2.17
Age
≤60	111	3.90±1.63	0.288	4.26±2.34	0.330
>60	231	4.11±1.73		4.52±2.33
Tumor location
Right colon	288	4.02±1.70	0.614	4.39±2.24	0.445
Left colon	54	4.15±1.70		4.65±2.42
Differentiation
Well/Moderate	128	3.27±1.60	<0.001	3.55±1.96	<0.001
Poor	214	4.50±1.58		4.96±2.27
Depth of invasion
Tis/T1/T2	47	3.46±1.69	0.012	3.67±1.90	0.012
T3/T4	295	4.13±1.68		4.56±2.30
Lymph node metastasis
No	106	3.67±1.54	0.006	3.78±2.02	<0.001
Yes	236	4.21±1.74		4.73±2.31
Distant metastasis
No	297	3.95±1.70	0.008	4.26±2.22	<0.001
Yes	45	4.66±1.57		5.5.8±2.2.8
TNM Stage
I/II	105	3.65±1.54	0.005	3.80±2.02	0.001
III/IV	237	4.21±1.74		4.72±2.31

Note: Bold values are statistically significant.

Figure 1 Immunohistochemical staining of RBP-Jκ and CXCL11 in colon cancer tissues and paratumorous tissues. (A–D) RBP-Jκ staining. (A) Paratumorous tissue. (B) Negative expression in colon cancer tissues. (C) Low expression in colon cancer tissues. (D) High expression in colon cancer tissues. (E–H) CXCL11 staining. (E) Paratumorous tissue. (F) Negative expression in colon cancer tissues. (G) Low expression in colon cancer tissues. (H) High expression in colon cancer tissues. Scale bar, 50μm.

Table 4 Association Between RBP-Jκ and CXCL11 in 342 Colon Cancer Patients

	CXCL11		r	P-value
	High	Low
RBP-Jκ
High	185	39	0.245	<0.001
Low	70	48

Figure 2 Correlation between RBP-Jκ and CXCL11 mRNA expression in colon cancer tissues. The dot plot figure shows a positive correlation between RBP-Jκ and CXCL11 mRNA expression (Pearson’s rank test r=0.220; P<0.001). X-axis: CXCL11 mRNA expression level of each patient. Y-axis: RBP-Jκ mRNA expression level of each patient.

Table 5 Univariate and Multivariate Analyses of 342 Colon Cancer Patients

Characteristics	n	Univariate Analysis		Multivariate Analysis
		HR (95% CI)	P-value	HR (95% CI)	P-value
Gender
Male	156	1	0.574
Female	186	0.917(0.678–1.240)
Age
≤60	111	1	0.004
>60	231	1.675(1.176–2.387)
Tumor location
Right colon	288	1	0.103
Left colon	54	1.382(0.936–2.040)
Differentiation
Well/Moderate	128	1	<0.001	1	<0.001
Poor	214	3.228(2.217–4.702)		2.966(2.022–4.352)
Depth of invasion
Tis/T1/T2	47	1	<0.001	1	0.009
T3/T4	295	3.893(1.914–7.919)		2.618(1.276–5.372)
Lymph node metastasis
No	106	1	<0.001
Yes	236	2.576(1.770–3.748)
Distant metastasis
No	297	1	<0.001	1	<0.001
Yes	45	4.014(2.792–5.772)		2.191(1.484–3.234)
TNM Stage
I/II	105	1	<0.001	1	<0.001
III/IV	237	2.614(1.790–3.818)		2.061(1.386–3.065)
RBP-Jκ
High	224	1	<0.001	1	0.036
Low	118	0.373(0.257–0.539)		0.655(0.441–0.972)
CXCL11
High	225	1	<0.001	1	0.001
Low	87	0.326(0.210–0.506)		0.441(0.278–0.700)

Note: Bold values are statistically significant.

Figure 3 Kaplan-Meier survival curves showing significantly different survival rates for patients with CRC according to RBP-Jκ and CXCL11 expression. (A) Survival curves for RBP-Jκ. (B) Survival curves for CXCL11. (C) Survival curves for all patients divided by the combination of RBP-Jκ and CXCL11 status. (D) Survival curves for RBP-Jκ high/CXCL11 high and other combinations of RBP-Jκ/CXCL11 expression.