CCR6 promotes liver metastasis of colorectal cancer through epithelial-mesenchymal transition

doi:10.3760/cma.j.issn.1673-422X.2020.01.005

Abstract

Abstract:

Objective To detect the expressions of chemokine receptor 6 (CCR6), CC chemokine ligand 20 (CCL20) E-cadherin and vimentin in tissues of colorectal cancer and their paired liver metastases, and to investigate the possible mechanism of CCR6 in liver metastasis of colorectal cancer. Methods A total of 62 cases (54 cases of colon cancer and 8 cases of rectal cancer) of primary colorectal adenocarcinoma resection with wax lumps were selected from the First Hospital of Shanxi Medical University and Shanxi Oncology Hospital from 2009 to 2017 with complete data, including 20 samples of colorectal cancer resection with liver metastasis during the same period. The expressions of CCR6, CCL20, E-cadherin and vimentin in colorectal cancer and liver metastases tissues were detected by immunohistochemistry, and the relationships between the expressions of CCR6, E-cadherin and vimentin and the clinicopathological features of patients were analyzed. Logistic multivariate regression was used to analyze the relationship between liver metastasis and clinicopathological features, CCR6, E-cadherin and vimentin. Spearman correlation was used to analyze the correlations between CCR6 and E-cadherin and vimentin. Results The positive expression rate of CCR6 in colorectal cancer tissues was 66.1% (41/62), 85.0% (17/20) in colorectal cancer with liver metastasis and 70.0% (14/20) in liver metastasis tissues. The positive expression rate of CCL20 in colorectal cancer tissues was 83.9% (52/62), 90.0% (18/20) in colorectal cancer with liver metastasis and 90.0% (18/20) in liver metastasis tissues. The positive expression rate of E-cadherin in colorectal cancer tissues was 67.7% (42/62), 50.0% (10/20) in colorectal cancer with liver metastasis and 65.0% (13/20) in liver metastasis tissues. The positive expression rate of vimentin in colorectal cancer tissues was 79.0% (49/62), 85.0% (17/20) in colorectal cancer with liver metastasis and 90.0% (18/20) in liver metastasis tissues. The expression of CCR6 was closely related to lymph node metastasis (χ ²=11.142, P=0.001), liver metastasis (χ ²=4.694, P=0.030) and TNM stage (χ ²=21.785, P<0.001). E-cadherin was closely related to lymph node metastasis (χ ²=4.694, P=0.030), liver metastasis (χ ²=4.253, P=0.039) and TNM stage (χ ²=7.867, P=0.005). Vimentin was closely related to lymph node metastasis (χ ²=7.293, P=0.007) and TNM stage (χ ²=5.712, P=0.017). CCR6, E-cadherin and vimentin were independent of gender, age, tumor site, tumor size and differentiation degree of colorectal cancer patients (all P>0.05). Logistic regression analysis showed that the expressions of CCR6 (OR=6.812, 95%CI: 1.206-38.474, P=0.030) and E-cadherin (OR=0.256, 95%CI: 0.069-0.945, P=0.041) were independent factors affecting the liver metastasis of colorectal cancer. Spearman correlation analysis showed that CCR6 was associated with E-cadherin expression (r=0.454, P=0.044) and vimentin expression (r=0.509, P=0.022) in 20 iver metastasis tissues of colorectal cancer. Conclusion CCR6 may promote colorectal cancer progress and liver metastasis by part of epithelial-mesenchymal transition.

Key words: Colorectal neoplasms, Receptors, CCR6, Cadherins, Vimentin, Liver metastasis

Zhang Haili, Li Juanfang, Li Xiaoqing, Shi Linjie, Li Yuanfei. CCR6 promotes liver metastasis of colorectal cancer through epithelial-mesenchymal transition[J]. Journal of International Oncology, 2020, 47(1): 29-34.

Figures/Tables 3

References 10

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临床病理特征	CCR6		χ²值	P值	E-钙黏着蛋白				χ²值		P值		波形蛋白		χ²值	P值
临床病理特征	+	-	χ²值	P值	+		-		χ²值		P值		+	-	χ²值	P值
性别
男	18	12	0.975	0.323	20		10		0.031		0.861		23	7	0.196	0.658
女	23	9			22		10						26	6
年龄(岁)
≤55	14	6	0.198	0.657	12		8		0.810		0.368		17	3	0.214	0.643
>55	27	15			30		12						32	10
肿瘤部位
结肠	36	18	0.000	1.000	35		19		0.767		0.381		42	12	0.027	0.869
直肠	5	3			7		1						7	1
肿瘤最大径(cm)
≤5	21	15	2.329	0.127	25		11		0.114		0.736		26	10	2.403	0.121
>5	20	6			17		9						23	3
有无淋巴结转移
无	8	13	11.142	0.001	18		3		4.694		0.030		12	9	7.293	0.007
有	33	8			24		17						37	4
有无肝转移
无	24	18	4.694	0.030	32		10		4.253		0.039		32	10	0.214	0.643
有	17	3			10		10						17	3
临床病理特征	CCR6		χ²值	P值		E-钙黏着蛋白				χ²值		P值	波形蛋白		χ²值	P值
临床病理特征	+	-	χ²值	P值		+		-		χ²值		P值	+	-	χ²值	P值
TNM分期
Ⅰ~Ⅱ期	8	17	21.785	<0.001		22		3		7.867		0.005	16	9	5.712	0.017
Ⅲ~Ⅳ期	33	4				20		17					33	4
分化程度
低分化	9	1	1.896	0.169		6		4		0.041		0.839	10	0	1.835	0.176
高中分化	32	20				36		16					39	13

参数	β值	SE值	Wald值	P值	OR值	95%CI
性别	0.465	0.661	0.495	0.482	1.592	0.436~5.811
年龄	-0.158	0.676	0.055	0.815	0.854	0.227~3.212
肿瘤部位	-1.011	1.176	0.739	0.390	0.364	0.036~3.645
肿瘤最大径	-0.300	0.682	0.193	0.660	0.741	0.195~2.820
分化程度	1.430	0.958	2.229	0.135	4.177	0.639~27.293
CCR6	1.919	0.883	4.717	0.030	6.812	1.206~38.474
E-钙黏着蛋白	-1.363	0.666	4.183	0.041	0.256	0.069~0.945
波形蛋白	-0.210	0.975	0.046	0.830	0.811	0.120~5.480

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