胃癌患者SFRP1、SFRP2、SDC-2甲基化与病理特征的相关性分析

黄一波; 王国平; 王奕; 莫文魁

doi:10.16766/j.cnki.issn.1674-4152.002222

胃癌患者SFRP1、SFRP2、SDC-2甲基化与病理特征的相关性分析

doi: 10.16766/j.cnki.issn.1674-4152.002222

浙江中医药大学附属二院普外科，浙江杭州 310005

基金项目:

浙江省医药卫生科技计划项目 2017KY517

详细信息

通讯作者:
王国平，E-mail：doctor9871@126.com

中图分类号: R735.2 R730.43
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出版历程
- 收稿日期: 2020-05-19
- 网络出版日期: 2022-03-02

Correlation analysis of SFRP1, SFRP2 and SDC-2 methylation and pathological features in patients with gastric cancer

Department of General Surgery, the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine, Hangzhou, Zhejiang 310005, China

摘要

摘要: 目的分析胃癌患者分泌型卷曲相关蛋白1(SFRP1)、SFRP2及多能体蛋白聚糖-2(SDC-2)基因甲基化与胃癌临床病理特征的相关性。方法收集浙江中医药大学附属二院在2017年5月—2019年4月收治的接受胃癌根治术的100例患者，检测胃癌组织中SFRP1、SFRP2及SDC-2基因甲基化状态；分析上述基因甲基化率在不同临床病理特征的胃癌组织中的差异。结果癌肿组织中SDC-2、SFRP1、SFRP2基因甲基化率、肿瘤直径、浸润深度、淋巴结转移及分化程度存在不同程度的差异(均P < 0.05)；多因素logistic回归分析显示，SDC-2甲基化(OR=0.384)是影响癌肿大小的独立保护因素(P < 0.05)；SFRP2甲基化(OR=5.991)是影响肿瘤浸润深度的独立危险因素，SDC-2甲基化(OR=0.171)是影响肿瘤浸润深度的独立保护因素(均P < 0.05)；SFRP1甲基化(OR=4.614)是影响肿瘤淋巴结转移的独立危险因素，SDC-2甲基化(OR=0.345)是抑制肿瘤淋巴结转移的独立保护性因素(均P < 0.05)；SFRP1甲基化(OR=11.667)、SFRP2甲基化(OR=23.333)是影响肿瘤分化程度的独立危险因素(均P < 0.05)。结论 SFRP1、SFRP2及SDC-2基因甲基化状态与胃癌患者临床病理特征存在高度相关性，SFRP1、SFRP2基因的甲基化可能是促进肿瘤增长、迁移、低分化的相关因素。
- 胃癌 /
- 分泌型卷曲相关蛋白基因 /
- 甲基化 /
- 病理特征
Abstract: Objective To analyse the correlation between secreted frizzled related protein 1(SFRP1), SFRP2 and SDC-2 gene methylation and clinicopathological characteristics of gastric cancer. Methods A total of 100 patients who underwent radical gastric cancer surgery from May 2017 to April 2019 in the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine were collected, and the methylation status of SFRP1, SFRP2 and SDC-2 genes in gastric cancer tissues was detected. The difference of the above-mentioned gene methylation rate in gastric cancer tissues with different clinicopathological characteristics was analysed. Results The methylation rates of SDC-2, SFRP1 and SFRP2 genes, tumor diameter, depth of invasion, lymph node metastasis and differentiation were different in cancer tissues (all P < 0.05). Multivariate logistic regression analysis showed that SDC-2 methylation (OR=0.384) was an independent protective factor affecting cancer size (P < 0.05). SFRP2 methylation (OR=5.991) was an independent risk factor affecting the depth of tumour invasion, whilst SDC-2 methylation (OR=0.171) was an independent protective factor affecting the depth of tumour invasion (all P < 0.05). SFRP1 methylation (OR=4.614) was an independent risk factor affecting tumour lymph node metastasis, whilst SDC-2 methylation (OR=0.345) was an independent protective factor inhibiting tumour lymph node metastasis (all P < 0.05). SFRP1 methylation (OR=11.667) and SFRP2 methylation (OR=23.333) were independent risk factors affecting tumour differentiation (all P < 0.05). Conclusion The methylation status of SFRP1, SFRP2 and SDC-2 genes is highly correlated with the clinicopathological characteristics of gastric cancer patients. The methylation of SFRP1 and SFRP2 genes may be related factors that promote tumour growth, migration and poor differentiation.
- Gastric cancer /
- Secreted frizzled related protein gene /
- Methylation /
- Pathological features

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表 1 SFRP1、SFRP2、SDC-2基因启动子区分析引物

基因名称	序列名称	引物序列(5'-3')	产物长度(bp)
SFRP1	甲基化引物(上游)	ATTTAGGTTTACGTGCGTTC	298
	甲基化引物(下游)	CGACTCAAAAACGAAAATCG
	非甲基化引物(上游)	TAGTATTAGTATTTAGGTTTATGTGTGTTT	318
	非甲基化引物(下游)	AACAACAATCCAACTCAAAAACAAAAATGA
SFRP2	甲基化引物(上游)	GCGGTTTCGTTGCGGTTTAC	140
	甲基化引物(下游)	GCCGACGCCGTTTCAAACCG
	非甲基化引物(上游)	GTGGTGTGGTGTGGTTTTGTTGTGGTTTAT	160
	非甲基化引物(下游)	ACACCCCCACACCAACACCATTTCAAACCA
SDC-2	甲基化引物(上游)	TCGTTTTGTTTTTAGGGGTC	187
	甲基化引物(下游)	GCAACCGCCTAAAAACGACG
	非甲基化引物(上游)	ATTTGGGTGGGTTGTTTTGTTTTTAGGGGTT	149
	非甲基化引物(下游)	ACACCCACCACAACCACCTAAAAACAACA

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表 2 不同临床病理特征之间SFRP1、SFRP2、SDC-2基因启动子区甲基化率比较[例(%)]

临床特征	例数	SFRP1			SFRP2			SDC2
临床特征	例数	甲基化	χ²值	P值	甲基化	χ²值	P值	甲基化	χ²值	P值
性别			0.246	0.619		0.011	0.916		0.418	0.518
男性	67	44(65.67)			46(68.66)			22(32.84)
女性	33	20(60.61)			23(69.70)			13(39.39)
年龄			0.090	0.764		1.823	0.177		0.113	0.737
< 65岁	52	34(65.38)			39(75.00)			19(36.54)
≥65岁	48	30(62.50)			30(62.50)			16(33.33)
肿瘤位置			0.199	0.905		0.929	0.628		0.023	0.988
贲门	22	14(63.64)			16(72.73)			8(36.36)
胃体	49	31(63.27)			35(71.43)			17(34.69)
胃窦	29	17(58.62)			18(62.07)			10(34.48)
组织学分型			8.833	0.012		9.814	0.007		0.112	0.945
低分化	35	29(82.86)			31(88.57)			12(34.29)
中分化	44	25(56.82)			25(56.82)			15(34.09)
高分化	21	10(47.62)			13(61.90)			8(38.10)
浸润深度			1.079	0.782		9.953	0.019		14.293	< 0.001
T1	19	14(73.68)			9(47.37)			13(68.42)
T2	33	21(63.64)			20(60.61)			12(36.36)
T3	27	16(59.26)			23(85.19)			7(25.93)
T4	21	13(61.90)			17(80.95)			3(14.29)
淋巴结转移			6.836	0.009		0.531	0.466		5.099	0.024
N0	24	10(41.67)			18(75.00)			13(54.17)
N1~N3	76	54(71.05)			51(67.11)			22(28.95)
肿瘤直径			0.801	0.371		0.199	0.655		5.069	0.024
<5 cm	42	29(69.05)			30(71.43)			20(47.62)
≥5 cm	58	35(60.34)			39(67.24)			15(25.86)

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表 3 变量赋值表

变量	赋值情况
组织学分型	低分化=1，高分化/中分化=0
浸润深度	T1~T2=0，T3~T4=1
淋巴结转移	N0=0，N1~N3=1
肿瘤直径	≥5 cm=1， < 5 cm=0
SFRP1	甲基化=1，未甲基化=0
SFRP2	甲基化=1，未甲基化=0
SDC-2	甲基化=1，未甲基化=0

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表 4 影响胃癌组织学分型的logistic回归分析

相关指标	B	SE	Wald χ²	P值	OR值	95% CI
SFRP1	2.457	0.585	17.628	< 0.001	11.667	3.706~36.729
SFRP2	3.150	0.713	19.491	< 0.001	23.333	5.763~94.469
SDC-2	-0.047	0.441	0.011	0.916	0.955	0.042~2.264
常量	-4.690	0.843	30.923	< 0.001	0.009

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表 5 影响胃癌组织浸润深度的logistic回归分析

相关指标	B	SE	Wald χ²	P值	OR值	95% CI
SFRP1	0.399	0.421	0.900	0.343	1.490	0.654~3.398
SFRP2	1.790	0.674	7.055	0.008	5.991	1.599~22.449
SDC-2	-1.765	0.655	7.271	0.007	0.171	0.047~0.617
常量	-1.516	0.752	4.059	0.044	0.220

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表 6 影响胃癌淋巴结转移的logistic回归分析

相关指标	B	SE	Wald χ²	P值	OR值	95% CI
SFRP1	1.529	0.634	5.825	0.016	4.614	1.333~15.970
SFRP2	0.554	0.701	0.625	0.429	1.740	0.441~6.872
SDC-2	-1.065	0.481	4.893	0.027	0.345	0.134~0.886
常量	-0.102	0.780	0.017	0.896	0.903

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表 7 影响胃癌肿瘤大小的logistic回归分析

相关指标	B	SE	Wald χ²	P值	OR值	95% CI
SFRP1	-1.198	1.146	1.093	0.296	0.302	0.032~2.851
SFRP2	0.927	1.177	0.620	0.431	2.526	0.251~25.385
SDC-2	-0.958	0.431	4.949	0.026	0.384	0.165~0.892
常量	0.460	0.369	1.553	0.213	1.583

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