The role of sFRP2 and Wnt /β-catenin pathway in the development and progression of colorectal cancer

doi:10.3877/cma.j.issn.2095-3224.2018.06.006

Abstract

Abstract:

Objective

To explore The role of sFRP2 and Wnt/β-catenin pathway in the development and progression of colorectal cancer.

Methods

Immunohistochemical staining was used to detect the expression of sFRP2 and β-catenin in colorectal cancer group and normal colorectal mucosa group, to detect the expression level and positive rate. The expression of sFRP2 gene in colorectal cancer cell line HCT116 was up-regulated by plasmid transfection, it was verified by Western blot. Then we conduct CCK-8 method, wound-healing assay and Transwell assay. Then the effects of up regulation of sFRP2 expression on cell proliferation, migration and invasion were analyzed.

Results

The results of immunohistochemistry showed that the positive rate of sFRP2 expression in normal colorectal mucosa is higher than colorectal cancer group (χ²=35.902, P=0.000); However, The rate of β-catenin membrane expression deficiency and ectopic expression in colorectal cancer group is higher than normal colorectal mucosa (χ²=23.149, P=0.000, χ²=27.002, P=0.000). The positive expression of sFRP2, the loss of expression and the ectopic expression of β-catenin membrane were significantly correlated with the differentiation of tumor tissues (χ²=5.420, P=0.020, χ²=6.472; P=0.011, χ²=7.158, P=0.007), however, it was not associated with sex, age, tumor location, tumor size, tumor stage and lymph node metastasis (P>0.05). The expression of sFRP2 was negatively correlated with β-catenin membrane expression deficiency and ectopic expression; There was a positive correlation between the β-catenin membrane expression deficiency and the ectopic expression. After plasmid transfection, the expression of sFRP2 and β-catenin significantly increased (t=25.430, P=0.001; t=15.000, P=0.001); The proliferation and migration rate of sFRP2 transfection group was significantly slower compared with the control group and the empty plasmid group (t=16.890, P=0.001; t=7.206, P=0.002); Compared with the control group, the number of transmembrane cells in sFRP2 transfected group was significantly fewer than that in the control group (t=25.459, P=0.001), and the cell invasion ability was significantly decreased.

Conclusion

The interaction between sFRP2 and Wnt/β-catenin pathway plays an important role in the development and progression of colorectal cancer. The up regulation of sFRP2 significantly inhibited the proliferation, migration and invasion of colorectal cancer cell line HCT116.

Key words: Colorectal neoplasms, sFRP2, β-catenin, HCT116

Youquan Shi, Yang Chong, Dong Tang, Qingquan Xiong, Yuqin Huang, Huaicheng Zhou, Qi Zhang, Zhixiang Jin, Daorong Wang. The role of sFRP2 and Wnt /β-catenin pathway in the development and progression of colorectal cancer[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2018, 07(06): 531-537.

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Figures/Tables 8

References 24

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特征		例数	sFRP2阳性表达	β-catenin异常表达
特征		例数	sFRP2阳性表达	膜表达缺失	异位表达
性别		?	?	?	?
?	男	18	5	10	12
?	女	14	4	7	7
χ²值		?	0.002	0.098	0.907
P值		?	0.960	0.755	0.341
年龄		?	?	?	?
?	<70	25	7	13	15
?	≥70	7	2	4	4
χ²值		?	0.001	0.058	0.019
P值		?	0.976	0.810	0.892
肿瘤部位		?	?	?	?
?	结肠	14	3	8	6
?	直肠	18	6	9	13
χ²值		?	0.552	0.161	2.815
P值		?	0.457	0.688	0.093
肿瘤大小		?	?	?	?
?	<5 cm	13	5	6	5
?	≥5 cm	19	4	11	14
χ²值		?	1.157	0.427	3.970
P值		?	0.282	0.513	0.071
肿瘤分期		?	?	?	?
?	Ⅰ/Ⅱ	17	6	10	11
?	Ⅲ/Ⅳ	15	3	7	8
χ²值		?	0.922	0.473	0.427
P值		?	0.337	0.492	0.513
组织分化		?	?	?	?
?	低分化	14	1	11	12
?	高中分化	18	8	6	7
χ²值		?	5.420	6.472	7.158
P值		?	0.020	0.011	0.007
淋巴结转移		?	?	?	?
?	无	12	5	5	8
?	有	20	4	12	11
χ²值		?	1.742	1.012	0.423
P值		?	0.187	0.314	0.515

特征		例数	sFRP2阳性表达	β-catenin异常表达
特征		例数	sFRP2阳性表达	膜表达缺失	异位表达
性别		?	?	?	?
?	男	18	5	10	12
?	女	14	4	7	7
χ²值		?	0.002	0.098	0.907
P值		?	0.960	0.755	0.341
年龄		?	?	?	?
?	<70	25	7	13	15
?	≥70	7	2	4	4
χ²值		?	0.001	0.058	0.019
P值		?	0.976	0.810	0.892
肿瘤部位		?	?	?	?
?	结肠	14	3	8	6
?	直肠	18	6	9	13
χ²值		?	0.552	0.161	2.815
P值		?	0.457	0.688	0.093
肿瘤大小		?	?	?	?
?	<5 cm	13	5	6	5
?	≥5 cm	19	4	11	14
χ²值		?	1.157	0.427	3.970
P值		?	0.282	0.513	0.071
肿瘤分期		?	?	?	?
?	Ⅰ/Ⅱ	17	6	10	11
?	Ⅲ/Ⅳ	15	3	7	8
χ²值		?	0.922	0.473	0.427
P值		?	0.337	0.492	0.513
组织分化		?	?	?	?
?	低分化	14	1	11	12
?	高中分化	18	8	6	7
χ²值		?	5.420	6.472	7.158
P值		?	0.020	0.011	0.007
淋巴结转移		?	?	?	?
?	无	12	5	5	8
?	有	20	4	12	11
χ²值		?	1.742	1.012	0.423
P值		?	0.187	0.314	0.515

组织类型	例数（例）	sFRP2阳性表达	β-catenin异常表达
组织类型	例数（例）	sFRP2阳性表达	膜表达缺失	异位表达
正常结直肠黏膜组	32	32（100）	0（0）	0（0）
结直肠癌组	32	9（28.1）	17（53.1）	19（59.4）
P值	?	<0.001^*	<0.001^*	<0.001^*

组织类型	例数（例）	sFRP2阳性表达	β-catenin异常表达
组织类型	例数（例）	sFRP2阳性表达	膜表达缺失	异位表达
正常结直肠黏膜组	32	32（100）	0（0）	0（0）
结直肠癌组	32	9（28.1）	17（53.1）	19（59.4）
P值	?	<0.001^*	<0.001^*	<0.001^*

分组	?	β-catenin膜表达缺失		β-catenin异位表达
?	?	＋	-	＋	-
sFRP2表达	＋	2	7	2	7
sFRP2表达	-	15	8	17	6
r值	?	-0.39	?	-0.47	?
P值	?	0.03	?	0.01	?
β-catenin异位表达	＋	14	5	?	?
β-catenin异位表达	-	3	10	?	?
r值	?	0.50	?	?	?
P值	?	0.004	?	?	?

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