口腔鳞状细胞癌中乙酰肝素酶、E-cadherin、N-cadherin的表达及其意义

戴思远; 蒋婕; 韩瑞; 徐锦程

doi:10.16766/j.cnki.issn.1674-4152.002495

口腔鳞状细胞癌中乙酰肝素酶、E-cadherin、N-cadherin的表达及其意义

doi: 10.16766/j.cnki.issn.1674-4152.002495

戴思远¹,
蒋婕²,
韩瑞²,
徐锦程^2, ,

1.
蚌埠医学院附属蚌埠第三人民医院口腔科，安徽蚌埠 233000
2.
蚌埠医学院第一附属医院口腔科，安徽蚌埠 233004

基金项目:

安徽高校自然科学研究项目 KJ2021ZD0088

详细信息

通讯作者:
徐锦程, E-mail: xjch9999@163.com

中图分类号: R739.8R730
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出版历程
- 收稿日期: 2022-02-09
- 网络出版日期: 2022-09-21

Expression and significance of heparanase, E-cadherin, and N-cadherin in oral squamous cell carcinoma

1.
Department of Stomatology, the Bengbu Third People's Hospital of Bengbu Medical College, Bengbu, Anhui 233000, China

摘要

摘要: 目的研究乙酰肝素酶(HPA)、上皮标记物E-钙黏蛋白(E-cadherin)、间质标记物N-钙黏蛋白(N-cadherin)在口腔鳞状细胞癌(OSCC)组织中的表达情况，探讨3种蛋白与OSCC临床病理特点的关系，以及这三者之间的关系。方法应用免疫组化法检测HPA、E-cadherin、N-cadherin蛋白在46例OSCC组织和15例正常口腔黏膜上皮中的表达情况。采用χ²检验，分析3种蛋白在OSCC中的表达情况，并检测其与OSCC临床病理特点的关系，再通过多因素二元logistic回归分析筛选独立影响因素，同时使用Spearman等级相关性分析，对三者表达的关系进行分析。结果 HPA在OSCC组织中的阳性表达率为73.9%，而在正常口腔黏膜上皮中则均为阴性表达(P＜0.001)。OSCC组织和正常口腔黏膜上皮组织中E-cadherin(56.5% vs. 93.3%)、N-cadherin(47.8% vs. 13.3%)的阳性表达率比较差异均有统计学意义(均P＜0.05)。不同临床分期、分化程度和有无淋巴结转移的患者HPA的阳性表达率比较差异有统计学意义(P＜0.05)。Logistic回归分析结果显示，临床分期、分化程度和有无淋巴结转移与HPA阳性表达有关。HPA和E-cadherin表达存在负相关性(r=-0.321，P＜0.05)，而与N-cadherin的表达存在正相关性(r=0.371，P＜0.05)。结论 HPA在OSCC组织中高表达，同时与OSCC的临床分期、分化程度、有无淋巴结转移有着密切的关系。HPA与E-cadherin的表达呈负相关，与N-cadherin的表达呈正相关，因此HPA的表达可促进OSCC的侵袭和转移，这种促进作用可能是通过HPA诱导OSCC组织发生了上皮间质转化(EMT)而实现的。
- 乙酰肝素酶 /
- 免疫组化 /
- 上皮间质转化 /
- 口腔鳞状细胞癌
Abstract: Objective To study the expression of heparanase (HPA), epithelial marker E-cadherin and interstitial marker N-cadherin in oral squamous cell carcinoma (OSCC), and to explore the relationship between the three proteins and the clinicopathological features of OSCC. Methods The protein levels of HPA, E-cadherin and N-cadherin were assessed in OSCC tissues from 46 patients and normal tissues from 15 controls by immunohistochemistry. χ² test was used to analyze the expression of three proteins in OSCC, and to detect the relationship between them and the clinicopathological characteristics of OSCC. Then the independent influencing factors were screened by multivariate binary logistic regression analysis. At the same time, Spearman rank correlation analysis was used to analyze the relationship between the expression of the three proteins. Results The positive expression rate of HPA in OSCC was 73.9%, while it was negative in normal oral mucosal epithelium (P < 0.001). There were significant differences in the positive expression rates of E-cadherin (56.5% vs. 93.3%) and N-cadherin (47.8% vs. 13.3%) between OSCC and normal oral mucosal epithelial tissues (all P < 0.05). There was significant difference in the positive expression rate of HPA in patients with different clinical stages, degrees of differentiation and lymph node metastasis (P < 0.05). Logistic regression analysis showed that clinical stage, degree of differentiation and lymph node metastasis were related to the positive expression of HPA. HPA expression was negatively correlated with E-cadherin expression (r=-0.321, P < 0.05), but it was positively correlated with N-cadherin expression (r=0.371, P < 0.05). Conclusion HPA is highly expressed in OSCC, which is closely related to the clinical stage, degree of differentiation and lymph node metastasis. HPA is negatively correlated with E-cadherin, but positively correlated with N-cadherin. The potential mechanism is that HPA may regulate epithelial interstitial transformation (EMT) in OSCC. Therefore, the expression of HPA can promote the invasion and metastasis of OSCC, and this effect may be achieved by HPA inducing epithelial mesenchymal transformation in OSCC.
- Heparanase /
- Immunohistochemistry /
- Epithelial-mesenchymal transition /
- Oral squamous cell carcinoma

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图 1 免疫组化染色HPA、E-cadherin、N-cadherin在不同组织类型中的表达(×200)

注：A、B、C分别为HPA、E-cadherin、N-cadherin蛋白在OSCC组织中的表达；D、E、F分别为HPA、E-cadherin、N-cadherin蛋白在正常口腔黏膜上皮中的表达。

Figure 1. Expression of HPA, E-cadherin and N- Cadherin in different tissues by immunohistochemical staining (×200)

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表 1 不同组织类型中HPA、E-cadherin、N-cadherin蛋白的表达情况[例(%)]

Table 1. Expression of HPA, E-cadherin and N-cadherin proteins in different tissue types [cases (%)]

组织类型	标本数	HPA	E-cadherin	N-cadherin
肿瘤组织	46	34(73.9)	26(56.5)	22(47.8)
正常黏膜	15	0	14(93.3)	2(13.3)
χ²值		25.048	6.790	5.639
P值		＜0.001	0.009	0.018

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表 2 OSCC组织中HPA的表达与临床病理特点的关系[例(%)]

Table 2. Relationship between HPA expression and clinicopathological features in OSCC tissues [cases (%)]

项目	例数	阳性	χ²值	P值
年龄(岁)			2.473	0.116
＜60	13	7(53.8)
≥60	33	27(81.8)
性别			0.423	0.516
男性	29	20(69.0)
女性	17	14(82.4)
吸烟			1.458	0.227
有	20	13(65.0)
无	26	21(80.8)
饮酒			0.104	0.747
有	25	18(72.0)
无	21	16(76.2)
临床分期			4.834	0.028
Ⅰ+Ⅱ	28	17(60.7)
Ⅲ+Ⅳ	18	17(94.4)
分化程度			4.046	0.044
高+中	34	22(64.7)
低+差	12	12(100.0)
淋巴结转移			5.291	0.008
有	14	14(100.0)
无	32	20(62.5)

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表 3 HPA表达的多因素二元logistic回归分析

Table 3. Multivariate binary logistic regression analysis of HPA expression

项目	β	SE	Wald χ²	P值	OR值	95% CI
Ⅲ+Ⅳ期	2.398	1.099	4.758	0.029	11.000	1.275~94.876
低+差分化	1.945	0.834	5.296	0.025	6.994	1.226~72.524
有淋巴结转移	1.198	1.102	3.028	0.032	3.134	1.193~59.094
注：赋值方法如下，临床分期Ⅰ+Ⅱ期=0，Ⅲ+Ⅳ期=1；分化程度高+中分化=0，低+差分化=1；无淋巴结转移=0，有淋巴结转移=1。

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表 4 OSCC组织中E-cadherin蛋白表达与临床病理特点的关系[例(%)]

Table 4. Correlation between E-cadherin protein expression and clinicopathological features in OSCC tissues [cases (%)]

项目	例数	阳性	χ²值	P值
年龄(岁)			0.186	0.667
＜60	13	8(61.5)
≥60	33	18(54.5)
性别			0.983	0.322
男性	29	18(62.1)
女性	17	8(47.1)
吸烟			0.174	0.676
有	20	12(60.0)
无	26	14(53.8)
饮酒			0.270	0.604
有	25	15(60.0)
无	21	11(52.4)
临床分期			6.470	0.011
Ⅰ+Ⅱ	28	20(71.4)
Ⅲ+Ⅳ	18	6(33.3)
分化程度			10.494	0.001
高+中	34	24(70.6)
低+差	12	2(16.7)
淋巴结转移			6.398	0.011
有	14	4(28.6)
无	32	22(68.8)

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表 5 E-cadherin表达的多因素二元logistic回归分析

Table 5. Multivariate binary logistic regression analysis of E-cadherin expression

项目	β	SE	Wald χ²	P值	OR值	95% CI
Ⅲ+Ⅳ期	-1.199	0.630	3.618	0.037	0.301	0.022~0.819
低+差分化	-3.018	1.114	7.334	0.007	0.049	0.006~0.434
有淋巴结转移	-1.234	0.671	3.389	0.066	0.291	0.012~0.617
注：赋值方法如下，临床分期Ⅰ+Ⅱ期=0，Ⅲ+Ⅳ期=1；分化程度高+中分化=0，低+差分化=1；无淋巴结转移=0，有淋巴结转移=1。

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表 6 OSCC组织中N-cadherin表达与临床病理特点的关系[例(%)]

Table 6. Correlation between N-cadherin expression and clinicopathological features in OSCC tissues [cases (%)]

项目	例数	阳性	χ²值	P值
年龄(岁)			2.113	0.146
＜60	13	4(30.8)
≥60	33	18(54.5)
性别			1.307	0.253
男性	29	12(41.4)
女性	17	10(58.8)
吸烟			0.067	0.796
有	20	10(50.0)
无	26	12(46.2)
饮酒			1.466	0.226
有	25	14(56.0)
无	21	8(38.1)
临床分期			14.941	＜0.001
Ⅰ+Ⅱ	28	7(25.0)
Ⅲ+Ⅳ	18	15(83.3)
分化程度			4.804	0.028
高+中	34	13(38.2)
低+差	12	9(75.0)
淋巴结转移			11.578	0.001
有	14	12(85.7)
无	32	10(31.3)

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表 7 N-cadherin表达的多因素二元logistic回归分析

Table 7. Multivariate binary logistic regression analysis of N-cadherin expression

项目	β	SE	Wald χ²	P值	OR值	95% CI
Ⅲ+Ⅳ期	2.708	0.768	12.420	＜0.001	14.999	3.327~67.636
低+差分化	2.768	1.110	6.220	0.013	15.923	1.809~140.164
有淋巴结转移	2.580	0.854	9.135	0.003	13.200	2.477~70.346
注：赋值方法如下，临床分期Ⅰ+Ⅱ期=0，Ⅲ+Ⅳ期=1；分化程度高+中分化=0，低+差分化=1；无淋巴结转移=0，有淋巴结转移=1。

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