胃癌组织中Ezrin、MMP-9的表达及与MVD关系的研究
摘要
胃癌是消化系统常见的恶性肿瘤,在我国其死亡率居各种癌症的首位。由于胃癌早期常无特异的症状,早期发现较为困难。相对于消化道其他恶性肿瘤,胃癌易发生淋巴道转移和血道转移,因而预后极差,5年生存率很低。
肿瘤转移是在基因调控下多因素参与、多阶段发展的复杂病理过程。现有的研究结果表明,此过程受肿瘤转移相关基因及转移抑制基因、血管和淋巴管生成因子、细胞表面的蛋白多糖、粘附分子、细胞外基质等多种因素的调控。
Ezrin蛋白是一种膜-细胞骨架连接蛋白,具有维持细胞形态和运动,连接黏附分子及调节信号转导等功能。通过对许多肿瘤组织的研究发现肿瘤组织中Ezrin蛋白的表达水平都显著高于正常组织,且肿瘤细胞中常有Ezrin蛋白亚细胞定位的改变;在一些转移能力较强的肿瘤细胞中,Ezrin蛋白常呈过表达。现有的研究认为Ezrin蛋白主要通过影响细胞粘附、肿瘤细胞信号转导、细胞凋亡和肿瘤细胞吞噬进而参与到肿瘤浸润和转移的各个环节。
基质金属蛋白酶(matrix metalloproteinases,MMPs)是一类锌离子依赖性蛋白酶家族,在体内其主要作用是降解细胞外基质,如间质胶原酶、明胶酶、间质溶素等,MMP-9是该家族中的重要一员。研究发现MMP-9活性上调与恶性肿瘤的浸润转移密切相关,可能是因为其被激活后降解细胞外基质,使肿瘤细胞脱落,导致肿瘤向周围组织浸润并侵入血管、淋巴管而远处转移。
肿瘤的生长和转移依赖于肿瘤血管生成。血管生成是肿瘤生长、浸润、转移和复发的基础,丰富的血管不仅增加了肿瘤细胞进入血循环的机率,而且肿瘤细胞还可侵入邻近与毛细血管伴行的淋巴管,促进淋巴道转移。微血管密度(microvessel density,MVD)可以指示肿瘤血管增殖情况,从而判断肿瘤的转移潜能。
有关Ezrin蛋白,MMP-9在胃癌中的表达及其与MVD关系的研究,迄今国内外尚未见报道。为此,本研究采用免疫组化SP法,分别检测了52例胃癌、31例癌旁不典型增生组织及21例正常胃黏膜组织中Ezrin蛋白、MMP-9的表达及MVD,并探讨了三者的相互关系。为进一步探讨胃癌的浸润转移机制及寻找有效地抑制胃癌浸润转移途径提供理论依据。
方法
1.采用免疫组化SP法检测Ezrin蛋白、MMP-9和CD105标记的MVD在正常胃黏膜(n=21)、不典型增生胃黏膜(n=31)及胃癌组织(n=52)中的表达。
2.统计学处理:所有数据均采用SPSS 10.0统计学软件进行统计学分析,阳性率之间的比较采用χ~2检验,两组资料均数之间比较用t检验;多组资料之间比较用单因素方差分析;两分类变量之间的关系分析采用spearman等级相关分析表示,以α=0.05为显著性检验水准。
结果
1.正常胃黏膜、癌旁不典型增生和胃癌组织中Ezrin蛋白的阳性表达率分别为4.8%(1/21),35.5%(11/31),63.5%(33/52);癌组织Ezrin蛋白阳性表达率与相应的癌旁不典型增生组织及正常胃黏膜组织两两相比,差异均有统计学意义(P＜0.01)。
2.侵及浅肌层、深肌层和浆膜层的胃癌组织中Ezrin蛋白阳性表达率分别为44.4%(8/18)、52.9%(9/17)和94.1%(16/17),侵及浆膜层的胃癌组织中Ezrin蛋白阳性表达率明显高于前两者,差异有统计学意义(P＜0.01),而侵及深肌层的胃癌组织中Ezrin蛋白阳性表达率与浅肌层组相比差异无统计学意义(P＞0.05)。
3.32例伴有淋巴结转移胃癌组织中Ezrin蛋白阳性表达率为81.3%(26/32);而无淋巴结转移20例胃癌组织中Ezrin蛋白的阳性表达率为35.0%(7/20),两组间胃癌组织Ezrin蛋白阳性表达率差异有统计学意义(P＜0.01)。
4.正常胃黏膜、癌旁不典型增生和胃癌组织中MMP-9蛋白阳性表达率分别为14.30%(3/21)、48.40%(15/31)和75.00%(39/52);癌组织MMP-9蛋白阳性表达率与相应的癌旁不典型增生组织及正常胃黏膜组织两两相比,差异均有统计学意义(P＜0.016)。
5.侵及浅肌层、深肌层和浆膜层的胃癌组织中MMP-9蛋白阳性表达率分别为44.4%(8/18)、58.8%(10/17)和94.1%(16/17)。侵及浆膜层的胃癌组织MMP-9蛋白阳性表达率明显高于前两者,差异有统计学意义(P＜0.016),侵及深肌层的胃癌组织中MMP-9蛋白阳性表达率与浅肌层组相比差异无有统计学意义(P＞0.05)。
6.32例伴有淋巴结转移胃癌组织中MMP-9蛋白阳性表达率为81.3%(26/32),而无淋巴结转移20例胃癌组织中MMP-9蛋白阳性表达率为40.00%(8/20),两组间胃癌组织MMP-9阳性表达率差异有统计学意义(P＜0.01)。
7.正常胃黏膜、癌旁不典型增生和胃癌组织中,CD105标记的MVD平均值分别为18.10±8.37、35.77±7.82和43.60±8.73,差异有统计学意义(P＜0.001)。癌组织MVD与相应的癌旁非典型增生组织及正常胃黏膜组织两两相比,差异均有统计学意义(P＜0.01)。
8.侵及浅肌层、深肌层和浆膜层的胃癌组织中,MVD平均值分别为35.89±6.07、43.18±6.91和52.18±3.28;侵及浆膜层的胃癌组织中MVD明显高于前两者,差异有统计学意义(P＜0.001)。
9.32例伴有淋巴结转移的胃癌组织中,MVD平均值为48.53±6.01,而无淋巴结转移的20例胃癌组织中,MVD平均值为35.70±6.11,两组相比,差异有统计学意义(P＜0.001)。
10.Ezrin蛋白与MMP-9在胃癌中表达的相关性经统计学分析显示呈显著正相关(P＜0.001);Ezrin蛋白阳性表达组的MVD平均值(47.52±7.72)高于阴性表达组(36.79±5.74),差异有统计学意义(P＜0.001);MMP-9蛋白阳性表达组的MVD平均值(47.62±7.35)高于阴性表达组(36.00±5.51),差异有统计学意义(P＜0.001)。
结论
1.Ezrin蛋白参与胃癌的发生发展过程并且与胃癌浸润、转移有关。
2.MMP-9蛋白参与胃癌的发生发展过程,MMP-9蛋白与胃癌浸润、转移有关。
3.胃癌组织中增生的微血管参与胃癌的发生发展并且与胃癌浸润、转移有关。
4.Ezrin蛋白、MMP-9蛋白以及胃癌组织中增生的新生血管三者在胃癌的发生、发展及浸润、转移过程中可能起协同作用。
Gastric carcinoma is a common malignant tumor of digestive system. In china, the morbidity of gastric carcinoma takes the first in various types of cancer. As a result of early Gastric carcinoma usually without specific symptoms, its early detection is very difficult, and because of Gastric carcinoma prone to metastasis by lymph and blood, its prognosis is extremely poor and 5-year survival rate is very low. Metastasis is a complex pathological process which is regulated by the gene, involved multi factors and developed with multi-stage. The existing research results show that this process is regulated by variety of factors such as tumor metastasis genes and metastasis suppressor gene, angiogenesis factors and lymphangiogenic factors, polysaccharides, adhesion molecules, extracellular matrix.
Ezrin is a membrane cytoskeleton cross linker protein which has the functions such as retain the cell morphology and movement, connect with adhesion molecules, and regulate signal transduction. A large number of research results have showed that the expression level of Ezrin protein in many tumor tissues was significantly higher than normal tissue. Ezrin protein was over-expression in the tumor cells that have the ability of metastasis, and often changed in subcellular localization in the tumor cells Ezrin protein mainly through regulating cell adhesion, signal transduction, apoptosis and phagocytosis of tumor cells to participate in all aspects of tumor metastasis and affect the infiltration and metastasis of tumors.
Matrix metalloproteinases (matrix metalloproteinases, MMPs) are a family of zinc dependent enzymes whose primary role is to degrade extracellular matrix, such as collagenase, gelatinases, and stromelysins. As one important member of the family, MMP-9 can degrade and destroy surface collagen and gelatin and result in infiltration and metastasis of tumor cells through damaged basement membrane to surrounding tissue.
Tumor's growth and metastasis depend on angiogenesis. Angiogenesis is the basis for tumor growth, invasion, metastasis and recurrence. Abundant vessels not only increase the invasive tumor cells' chances of entering the blood circulation, and also promote lymphatic metastasis. Micro vessel density (micro vessel density, MVD) can show the proliferation of tumor angiogenesis and estimate the tumor's metastatic potential.
It has not been reported that the expression of Ezrin and MMP-9 in gastric cancer and its relationship with MVD so far at home and abroad. In order to discuss the mechanisms of infiltration and metastasis of gastric carcinoma and search valid methods which can suppress the infiltration and metastasis of gastric carcinoma, this research adopts immunohistochemistry SP method to observe the expression of Ezrin, MMP-9 and MVD in 52 cases of gastric carcinoma tissues, 31 cases of non-atypical hyperplasia tissues and 21 cases of normal mucosa tissues.
Methods
1. Using the immunohistochemistry SP technology to detect the expression of Ezrin、MMP-9 and MVD in the 52 cases of gastric carcinoma, 31 cases of atypical hyperplasia tissues and 21 cases of normal mucosa of gastric carcinoma respectively.
2. Statistical analysis: All the data were analyzed by SPSS 10.0 statistical package. The Chi-square was used in the comparison of positive rates; the t-test was used in the comparison of means between two groups; the One-Way ANOVA was used in the comparison of means between three groups; the relation of two variables was analyzed by the spearman level correlation analysis. The level of significant difference wasα=0.05.
Results
1. The positive expression rates of Ezrin protein in normal mucosa of stomach, atypical hyperplasia tissues, and carcinoma tissues were 4.8% (1/21), 35.5% (11/31) and 63.5%(33 /52) respectively; the positive expression rate of Ezrin protein in the carcinoma tissues was compared with that in the atypical hyperplasia tissues and normal mucosa tissues from each other, and there was statistical significance (P <0.01).
2. In the tissues of gastric carcinoma, the positive rates of expression of Ezrin protein on the low-muscle invaded, deep-muscle invaded and outer layer invaded were 44.4% (8/18), 52.9% (9/17) and 94.1% (16/17) respectively. The expression of Ezrin in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups (P<0.01). Thus the expression of Ezrin in the carcinoma tissues with deep-muscle was compared with that with low-muscle, and there was no significance (P>0.05).
3. In the 32 cases of metastatic group, the positive rate of expression of Ezrin protein in the tumor tissues was 81.3% (26/32); in the non-metastatic group, it was 35.0% (7/20). There was significant difference between the two groups (P<0.01).
4. The positive expression rates of MMP-9 protein in normal mucosa of stomach , atypical hyperplasia tissues, and carcinoma tissues were 14.30% (3/21), 48.40% (15/31) and 75.00% (39/52) respectively; the positive expression rate of MMP-9 protein in the carcinoma tissues was compared with that in the atypical hyperplasia tissues and normal mucosa tissues from each other, and there was statistical significance(P<0.016).
5. In the tissues of gastric carcinoma, the positive rates of expression of MMP-9 protein on the low-muscle invaded, deep-muscle invaded and outer layer invaded were 44.4% (8/18),58.8% (10/17) and 94.1% (16/17) respectively. The expression of MMP-9 in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups (P<0.05). Thus the expression of MMP-9 in the carcinoma tissues with deep-muscle was compared with that with low-muscle, and there was no significance (P>0.05).
6. In the 32 cases of metastatic group, the positive rate of expression of MMP-9 protein in the tumor tissues was 81.3% (26/32); in the non-metastatic group, it was 40.00% (8/20). There was significant difference between the two groups (P<0.01).
7. The means of MVD in normal mucosa of stomach, atypical hyperplasia tissues and carcinoma tissues were 18.10±8.37,35.77±7.82 and 43.60±8.73 respectively, the means of MVD in the carcinoma tissues was compared with that in the atypical hyperplasia tissues and normal mucosa tissues from each other, and there was statistical significance(P<0.01).
8. In the tissues of gastric carcinoma, the means of MVD in the low-muscle invaded, deep-muscle invaded and outer layer invaded were 35. 89±6. 07、43.18±6. 91 and 52. 18±3. 28 respectively. The mean of MVD in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups (P<0.001).
9. In the 32 cases of metastatic group, the mean of MVD in the tumor tissues was 48.53±6.01; in the non-metastatic group, it was 48.53±6.01. There was significant difference between the two groups (P<0.001).
10. The relativity of the expression of Ezrin and MMP-9 in gastric carcinoma was analyzed statistically. Results showed that the expression of Ezrin was positively correlated with that of MMP-9(P<0.01); the mean of MVD in the carcinoma tissues with the positive expression of Ezrin protein(47.52±7.72) was evidently higher than that in the tissue with the negative expression of Ezrin protein (36.79±5.74) . There was significant difference among the groups (P<0.001). The mean of MVD in the carcinoma tissues with the positive expression of MMP-9 protein (47.62±7.35) was evidently higher than that in the tissue with the negative expression of MMP-9 protein(36.00±5.51) . There was significant difference among the groups (P<0.001).
Conclusions
1. Ezrin participates in occurrence and development of gastric carcinoma and also in infiltration and metastasis of gastric carcinoma.
2. MMP-9 participates in occurrence and development of gastric carcinoma and also in infiltration and metastasis of gastric carcinoma.
3. Micro vessel proliferation participates in occurrence and development of gastric carcinoma. Also Micro vessel proliferation participates in infiltration and metastasis of gastric carcinoma.
4. Ezrin, MMP-9 and the Micro vessel may play a synergistic effect during the process of occurrence and development and infiltration, metastasis of gastric carcinoma.
肿瘤转移是在基因调控下多因素参与、多阶段发展的复杂病理过程。现有的研究结果表明,此过程受肿瘤转移相关基因及转移抑制基因、血管和淋巴管生成因子、细胞表面的蛋白多糖、粘附分子、细胞外基质等多种因素的调控。
Ezrin蛋白是一种膜-细胞骨架连接蛋白,具有维持细胞形态和运动,连接黏附分子及调节信号转导等功能。通过对许多肿瘤组织的研究发现肿瘤组织中Ezrin蛋白的表达水平都显著高于正常组织,且肿瘤细胞中常有Ezrin蛋白亚细胞定位的改变;在一些转移能力较强的肿瘤细胞中,Ezrin蛋白常呈过表达。现有的研究认为Ezrin蛋白主要通过影响细胞粘附、肿瘤细胞信号转导、细胞凋亡和肿瘤细胞吞噬进而参与到肿瘤浸润和转移的各个环节。
基质金属蛋白酶(matrix metalloproteinases,MMPs)是一类锌离子依赖性蛋白酶家族,在体内其主要作用是降解细胞外基质,如间质胶原酶、明胶酶、间质溶素等,MMP-9是该家族中的重要一员。研究发现MMP-9活性上调与恶性肿瘤的浸润转移密切相关,可能是因为其被激活后降解细胞外基质,使肿瘤细胞脱落,导致肿瘤向周围组织浸润并侵入血管、淋巴管而远处转移。
肿瘤的生长和转移依赖于肿瘤血管生成。血管生成是肿瘤生长、浸润、转移和复发的基础,丰富的血管不仅增加了肿瘤细胞进入血循环的机率,而且肿瘤细胞还可侵入邻近与毛细血管伴行的淋巴管,促进淋巴道转移。微血管密度(microvessel density,MVD)可以指示肿瘤血管增殖情况,从而判断肿瘤的转移潜能。
有关Ezrin蛋白,MMP-9在胃癌中的表达及其与MVD关系的研究,迄今国内外尚未见报道。为此,本研究采用免疫组化SP法,分别检测了52例胃癌、31例癌旁不典型增生组织及21例正常胃黏膜组织中Ezrin蛋白、MMP-9的表达及MVD,并探讨了三者的相互关系。为进一步探讨胃癌的浸润转移机制及寻找有效地抑制胃癌浸润转移途径提供理论依据。
方法
1.采用免疫组化SP法检测Ezrin蛋白、MMP-9和CD105标记的MVD在正常胃黏膜(n=21)、不典型增生胃黏膜(n=31)及胃癌组织(n=52)中的表达。
2.统计学处理:所有数据均采用SPSS 10.0统计学软件进行统计学分析,阳性率之间的比较采用χ~2检验,两组资料均数之间比较用t检验;多组资料之间比较用单因素方差分析;两分类变量之间的关系分析采用spearman等级相关分析表示,以α=0.05为显著性检验水准。
结果
1.正常胃黏膜、癌旁不典型增生和胃癌组织中Ezrin蛋白的阳性表达率分别为4.8%(1/21),35.5%(11/31),63.5%(33/52);癌组织Ezrin蛋白阳性表达率与相应的癌旁不典型增生组织及正常胃黏膜组织两两相比,差异均有统计学意义(P＜0.01)。
2.侵及浅肌层、深肌层和浆膜层的胃癌组织中Ezrin蛋白阳性表达率分别为44.4%(8/18)、52.9%(9/17)和94.1%(16/17),侵及浆膜层的胃癌组织中Ezrin蛋白阳性表达率明显高于前两者,差异有统计学意义(P＜0.01),而侵及深肌层的胃癌组织中Ezrin蛋白阳性表达率与浅肌层组相比差异无统计学意义(P＞0.05)。
3.32例伴有淋巴结转移胃癌组织中Ezrin蛋白阳性表达率为81.3%(26/32);而无淋巴结转移20例胃癌组织中Ezrin蛋白的阳性表达率为35.0%(7/20),两组间胃癌组织Ezrin蛋白阳性表达率差异有统计学意义(P＜0.01)。
4.正常胃黏膜、癌旁不典型增生和胃癌组织中MMP-9蛋白阳性表达率分别为14.30%(3/21)、48.40%(15/31)和75.00%(39/52);癌组织MMP-9蛋白阳性表达率与相应的癌旁不典型增生组织及正常胃黏膜组织两两相比,差异均有统计学意义(P＜0.016)。
5.侵及浅肌层、深肌层和浆膜层的胃癌组织中MMP-9蛋白阳性表达率分别为44.4%(8/18)、58.8%(10/17)和94.1%(16/17)。侵及浆膜层的胃癌组织MMP-9蛋白阳性表达率明显高于前两者,差异有统计学意义(P＜0.016),侵及深肌层的胃癌组织中MMP-9蛋白阳性表达率与浅肌层组相比差异无有统计学意义(P＞0.05)。
6.32例伴有淋巴结转移胃癌组织中MMP-9蛋白阳性表达率为81.3%(26/32),而无淋巴结转移20例胃癌组织中MMP-9蛋白阳性表达率为40.00%(8/20),两组间胃癌组织MMP-9阳性表达率差异有统计学意义(P＜0.01)。
7.正常胃黏膜、癌旁不典型增生和胃癌组织中,CD105标记的MVD平均值分别为18.10±8.37、35.77±7.82和43.60±8.73,差异有统计学意义(P＜0.001)。癌组织MVD与相应的癌旁非典型增生组织及正常胃黏膜组织两两相比,差异均有统计学意义(P＜0.01)。
8.侵及浅肌层、深肌层和浆膜层的胃癌组织中,MVD平均值分别为35.89±6.07、43.18±6.91和52.18±3.28;侵及浆膜层的胃癌组织中MVD明显高于前两者,差异有统计学意义(P＜0.001)。
9.32例伴有淋巴结转移的胃癌组织中,MVD平均值为48.53±6.01,而无淋巴结转移的20例胃癌组织中,MVD平均值为35.70±6.11,两组相比,差异有统计学意义(P＜0.001)。
10.Ezrin蛋白与MMP-9在胃癌中表达的相关性经统计学分析显示呈显著正相关(P＜0.001);Ezrin蛋白阳性表达组的MVD平均值(47.52±7.72)高于阴性表达组(36.79±5.74),差异有统计学意义(P＜0.001);MMP-9蛋白阳性表达组的MVD平均值(47.62±7.35)高于阴性表达组(36.00±5.51),差异有统计学意义(P＜0.001)。
结论
1.Ezrin蛋白参与胃癌的发生发展过程并且与胃癌浸润、转移有关。
2.MMP-9蛋白参与胃癌的发生发展过程,MMP-9蛋白与胃癌浸润、转移有关。
3.胃癌组织中增生的微血管参与胃癌的发生发展并且与胃癌浸润、转移有关。
4.Ezrin蛋白、MMP-9蛋白以及胃癌组织中增生的新生血管三者在胃癌的发生、发展及浸润、转移过程中可能起协同作用。
Gastric carcinoma is a common malignant tumor of digestive system. In china, the morbidity of gastric carcinoma takes the first in various types of cancer. As a result of early Gastric carcinoma usually without specific symptoms, its early detection is very difficult, and because of Gastric carcinoma prone to metastasis by lymph and blood, its prognosis is extremely poor and 5-year survival rate is very low. Metastasis is a complex pathological process which is regulated by the gene, involved multi factors and developed with multi-stage. The existing research results show that this process is regulated by variety of factors such as tumor metastasis genes and metastasis suppressor gene, angiogenesis factors and lymphangiogenic factors, polysaccharides, adhesion molecules, extracellular matrix.
Ezrin is a membrane cytoskeleton cross linker protein which has the functions such as retain the cell morphology and movement, connect with adhesion molecules, and regulate signal transduction. A large number of research results have showed that the expression level of Ezrin protein in many tumor tissues was significantly higher than normal tissue. Ezrin protein was over-expression in the tumor cells that have the ability of metastasis, and often changed in subcellular localization in the tumor cells Ezrin protein mainly through regulating cell adhesion, signal transduction, apoptosis and phagocytosis of tumor cells to participate in all aspects of tumor metastasis and affect the infiltration and metastasis of tumors.
Matrix metalloproteinases (matrix metalloproteinases, MMPs) are a family of zinc dependent enzymes whose primary role is to degrade extracellular matrix, such as collagenase, gelatinases, and stromelysins. As one important member of the family, MMP-9 can degrade and destroy surface collagen and gelatin and result in infiltration and metastasis of tumor cells through damaged basement membrane to surrounding tissue.
Tumor's growth and metastasis depend on angiogenesis. Angiogenesis is the basis for tumor growth, invasion, metastasis and recurrence. Abundant vessels not only increase the invasive tumor cells' chances of entering the blood circulation, and also promote lymphatic metastasis. Micro vessel density (micro vessel density, MVD) can show the proliferation of tumor angiogenesis and estimate the tumor's metastatic potential.
It has not been reported that the expression of Ezrin and MMP-9 in gastric cancer and its relationship with MVD so far at home and abroad. In order to discuss the mechanisms of infiltration and metastasis of gastric carcinoma and search valid methods which can suppress the infiltration and metastasis of gastric carcinoma, this research adopts immunohistochemistry SP method to observe the expression of Ezrin, MMP-9 and MVD in 52 cases of gastric carcinoma tissues, 31 cases of non-atypical hyperplasia tissues and 21 cases of normal mucosa tissues.
Methods
1. Using the immunohistochemistry SP technology to detect the expression of Ezrin、MMP-9 and MVD in the 52 cases of gastric carcinoma, 31 cases of atypical hyperplasia tissues and 21 cases of normal mucosa of gastric carcinoma respectively.
2. Statistical analysis: All the data were analyzed by SPSS 10.0 statistical package. The Chi-square was used in the comparison of positive rates; the t-test was used in the comparison of means between two groups; the One-Way ANOVA was used in the comparison of means between three groups; the relation of two variables was analyzed by the spearman level correlation analysis. The level of significant difference wasα=0.05.
Results
1. The positive expression rates of Ezrin protein in normal mucosa of stomach, atypical hyperplasia tissues, and carcinoma tissues were 4.8% (1/21), 35.5% (11/31) and 63.5%(33 /52) respectively; the positive expression rate of Ezrin protein in the carcinoma tissues was compared with that in the atypical hyperplasia tissues and normal mucosa tissues from each other, and there was statistical significance (P <0.01).
2. In the tissues of gastric carcinoma, the positive rates of expression of Ezrin protein on the low-muscle invaded, deep-muscle invaded and outer layer invaded were 44.4% (8/18), 52.9% (9/17) and 94.1% (16/17) respectively. The expression of Ezrin in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups (P<0.01). Thus the expression of Ezrin in the carcinoma tissues with deep-muscle was compared with that with low-muscle, and there was no significance (P>0.05).
3. In the 32 cases of metastatic group, the positive rate of expression of Ezrin protein in the tumor tissues was 81.3% (26/32); in the non-metastatic group, it was 35.0% (7/20). There was significant difference between the two groups (P<0.01).
4. The positive expression rates of MMP-9 protein in normal mucosa of stomach , atypical hyperplasia tissues, and carcinoma tissues were 14.30% (3/21), 48.40% (15/31) and 75.00% (39/52) respectively; the positive expression rate of MMP-9 protein in the carcinoma tissues was compared with that in the atypical hyperplasia tissues and normal mucosa tissues from each other, and there was statistical significance(P<0.016).
5. In the tissues of gastric carcinoma, the positive rates of expression of MMP-9 protein on the low-muscle invaded, deep-muscle invaded and outer layer invaded were 44.4% (8/18),58.8% (10/17) and 94.1% (16/17) respectively. The expression of MMP-9 in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups (P<0.05). Thus the expression of MMP-9 in the carcinoma tissues with deep-muscle was compared with that with low-muscle, and there was no significance (P>0.05).
6. In the 32 cases of metastatic group, the positive rate of expression of MMP-9 protein in the tumor tissues was 81.3% (26/32); in the non-metastatic group, it was 40.00% (8/20). There was significant difference between the two groups (P<0.01).
7. The means of MVD in normal mucosa of stomach, atypical hyperplasia tissues and carcinoma tissues were 18.10±8.37,35.77±7.82 and 43.60±8.73 respectively, the means of MVD in the carcinoma tissues was compared with that in the atypical hyperplasia tissues and normal mucosa tissues from each other, and there was statistical significance(P<0.01).
8. In the tissues of gastric carcinoma, the means of MVD in the low-muscle invaded, deep-muscle invaded and outer layer invaded were 35. 89±6. 07、43.18±6. 91 and 52. 18±3. 28 respectively. The mean of MVD in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups (P<0.001).
9. In the 32 cases of metastatic group, the mean of MVD in the tumor tissues was 48.53±6.01; in the non-metastatic group, it was 48.53±6.01. There was significant difference between the two groups (P<0.001).
10. The relativity of the expression of Ezrin and MMP-9 in gastric carcinoma was analyzed statistically. Results showed that the expression of Ezrin was positively correlated with that of MMP-9(P<0.01); the mean of MVD in the carcinoma tissues with the positive expression of Ezrin protein(47.52±7.72) was evidently higher than that in the tissue with the negative expression of Ezrin protein (36.79±5.74) . There was significant difference among the groups (P<0.001). The mean of MVD in the carcinoma tissues with the positive expression of MMP-9 protein (47.62±7.35) was evidently higher than that in the tissue with the negative expression of MMP-9 protein(36.00±5.51) . There was significant difference among the groups (P<0.001).
Conclusions
1. Ezrin participates in occurrence and development of gastric carcinoma and also in infiltration and metastasis of gastric carcinoma.
2. MMP-9 participates in occurrence and development of gastric carcinoma and also in infiltration and metastasis of gastric carcinoma.
3. Micro vessel proliferation participates in occurrence and development of gastric carcinoma. Also Micro vessel proliferation participates in infiltration and metastasis of gastric carcinoma.
4. Ezrin, MMP-9 and the Micro vessel may play a synergistic effect during the process of occurrence and development and infiltration, metastasis of gastric carcinoma.
引文
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2.Atsumura S,Oue N,Nakayama H,et al.A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer[J].J Cancer Res Clin Oricol,2005;131(1):19-25.
3.Tian B,Li Y,Ji XN,et al.Basement membrane proteins play an active role in the invasive process of human hepatocellular Carcinoma cells with high metastasis potential[J].J Cancer Res Clin Oricol,2005;131(2):80-86
4.TIAN G,LI Q.Relationship between invasiveness and angiogenesis in human pituitary adenomas[J].China Journal of Modern Medicine,2003,13(8):31-34.
5.YAO LQ,JI TH.Correlation of tumor microvessel density with prognosis in extralymphonodal Ki-1 positive anaplastic large cell lymphoma.[J].The Practical Journal of Cancer,2002,17(5):31-34.
6.Mathew J,Hines J E,Obafunwa J O,et al.CD44 is exp ressed in heap to cellular carcinomas showing vascular invasion[J].J Pathol,1996,179(10):74-79.
7.Weidner N,Folkman J,Pozza F,et al.Tumor angiogenesis:a new significant and independent prognostic indicator in early-stage breast carcinoma.[J].Natl Cancer Inst,1992,84:1875-1887.
8.李晟磊,刘宗文,赵秋民等。食管鳞癌组织中RECK mRNA和蛋白的表达及意义[J].中国肿瘤临床,2007,34(22)1280-1286。
9.Bretscher A.Microfilament organization in the cytoskeleton of the intestinal brush border[J].Cell Muscle Motil,1983,4(2):239-268.
10.Bretscher A.Purification of an 80 000-dalton protein that is a component of the isolated microvillus cytoskeleton,and its localization in non muscle cells[J].J Cell Biol,1983,97(2):425-432.
11.Moilanen J,Lassus H,Leminen A,et al.Ezrin immunoreactivity in relation to survival in serous ovarian carcinoma patients[J].Gynecol Oncol,2003,90(2):273-281.
12.Zhang Y,Hu MY,Wu WZ,et al.The membrane- cytoskeleton organizer ezrin is necessary for hepatocellular carcinoma cell growth and invasiveness[J].J Cancer Res ClinOncol,2006,132(11):685-697.
13.A kisawa N,Nishimori I,Lwamura T,et al.High levels of ezrin expressed by human pancreatic adenocarcinoma cell lines with high metastatic potential[J].Biochem Biophys Res Commun,1999,258(2):395-400.
14.Duffy MJ,McGowan PM,Gallagher WM.Cancer invasion and metastasis:changing views[J].J Pathol,2008,214(3):289-293.
15.侯振江,张宗英,单保恩.基质金属蛋白酶在肝癌研究中的进展[J].国外医学临床生物化学与检验学分册,2005,26(8):517-519。
16.Rao JS,Bhoopathi P,Chetty C,et al.MMP-9 short interfering RNA induced senescence resulting in inhibition of medulloblastoma growth via.p16(INK4a)and mitogen-activated protein kinase pathway[J].Cancer Res 2007,67(10):4956-4964.
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