CD44v6和FOXD3在人胃癌组织中的表达及临床意义

发布时间：2018-06-30 04:32

本文选题：CD44v6 + FOXD3　；参考：《安徽医科大学》2015年硕士论文

【摘要】：目的:研究肿瘤干细胞标志物CD44v6和干细胞关键转录因子FOXD3蛋白在胃癌及其癌旁正常组织中的表达,分析两者与胃癌患者临床病理参数间的关系,探讨两种蛋白与胃癌浸润、转移以及预后等生物学行为的关系;通过研究肿瘤干细胞标志物CD44v6在胃癌组织中的表达情况,以及对FOXD3与CD44v6蛋白表达的相关性的统计分析,探讨FOXD3作为胃癌干细胞标志物的可能性。方法:第一部分:收集胃癌手术切除标本100例,其中高分化腺癌11例,中分化腺癌38例,低分化腺癌51例(包括粘液细胞癌、粘液腺癌)和癌旁正常胃黏膜组织40例,结合免疫组织化学方法(Envision二步法)对CD44v6和FOXD3蛋白的表达进行检测,对两者与胃癌临床病理参数间的关系进行统计分析,并且分析两者之间的相关性。第二部分:选取1982-2002年美国弗吉尼亚大学医学院病理系胃癌存档病例125例,以及安徽医科大学第一附属医院病理科胃癌切除手术标本60例,共185例,将上述两组胃癌标本分别制成2张胃癌组织芯片,结合免疫组织化学方法(Envision二步法)对CD44v6和FOXD3的表达进行检测,分析两者与胃癌患者临床病理参数间的关系以及两者之间的相关性,并且与第一部分结果进行对比。结果:第一部分、在传统病理切片标本中的表达:(1)CD44v6蛋白在胃癌组织的阳性表达率为88%(88/100),明显高于其在癌旁正常胃黏膜组织的阳性率22.5%(9/40),差异具有显著统计学意义(χ2=57.601,P0.001);CD44v6在胃癌组织中的表达水平与胃癌的分化程度、浸润深度、淋巴结转移、临床TNM分期具有明显相关性(P0.05),与患者的性别、年龄以及肿瘤直径均无相关性(P0.05);(2)FOXD3蛋白在胃癌组织的阳性表达率为22%(22/100)明显低于其在癌旁正常胃黏膜组织中阳性表达率90%(36/40),差异具有显著统计学意义(χ2=49.694,P0.001);FOXD3蛋白在胃癌组织中的表达水平与胃癌的分化程度、浸润深度、淋巴结转移、临床TNM分期具有明显相关性(P0.05),与患者的性别、年龄以及肿瘤直径均无相关性(P0.05);(3)在胃癌组织中,CD44v6蛋白和FOXD3蛋白的表达呈显著负相关(rs=-0.276,P0.01)。第二部分、在组织芯片中的表达:(1)CD44v6蛋白在胃癌组织中阳性率为47.27%(52/110),明显高于其在癌旁正常组织的阳性表达率22.5%(9/40),两者具有明显统计学差异(χ2=7.461,P0.01);CD44v6在胃癌组织中的表达水平与胃癌的浸润深度、淋巴结转移、临床TNM分期具有明显相关性(P0.05),与患者的性别、年龄、肿瘤直径以及分化程度均无相关性(P0.05);除分化程度方面的差异外,此结果与第一部分结果一致。(2)FOXD3蛋白在胃癌组织中阳性率为30.91%(34/110),明显低于FOXD3蛋白在癌旁正常胃黏膜组织中的阳性表达率90.0%(36/40),差异有显著统计学意义(χ2=36.747,P0.001);FOXD3在胃癌组织中的表达水平与胃癌的浸润深度、淋巴结转移、临床TNM分期具有明显相关性(P0.05),与患者的性别、年龄、肿瘤直径以及分化程度均无相关性(P0.05);除分化程度方面的差异外,此结果与第一部分结果一致;(3)在胃癌组织中,CD44v6蛋白和FOXD3蛋白的表达呈显著负相关(rs=-0.583,P0.001)。结论:(1)CD44v6作为胃癌干细胞肿瘤标记物,其与肿瘤的浸润、转移以及预后等生物学行为的关系密切。(2)FOXD3作为干细胞关键转录因子,其与肿瘤的浸润、转移以及预后等生物学行为的关系密切。(3)CD44v6与FOXD3蛋白的表达呈显著负相关,两者在胃癌的发生发展和侵袭转移中可能是相互制约的。FOXD3可能也为胃癌干细胞肿瘤标记物。(4)组织芯片为高通量、高效检测的临床组织样本,与传统切片标本相比具有快速、经济、省时、省力的特点。
[Abstract]:Objective: To study the expression of tumor stem cell marker CD44v6 and key transcription factor FOXD3 protein in the normal tissues of gastric cancer and its adjacent cancer, analyze the relationship between the two and the clinicopathological parameters of gastric cancer patients, and explore the relationship between the two proteins and the biological behavior of gastric cancer infiltration, metastasis and prognosis, and the study of tumor stem cell markers. The expression of CD44v6 in gastric carcinoma and the statistical analysis of the correlation between the expression of FOXD3 and CD44v6 protein and the possibility of FOXD3 as a marker of gastric cancer stem cells. Methods: the first part: collecting 100 cases of gastric cancer resection, of which 11 cases of highly differentiated adenocarcinoma, 38 cases of middle differentiated adenocarcinoma, and 51 cases of low differentiated adenocarcinoma (including mucus adenocarcinoma). 40 cases of liquid cell carcinoma, mucous adenocarcinoma) and normal gastric mucosa adjacent to cancer, combined with immunohistochemical method (Envision two step method) to detect the expression of CD44v6 and FOXD3 protein. The relationship between the two and the clinicopathological parameters of gastric cancer was statistically analyzed, and the correlation between the two was analyzed. The second part: 1982-2002 years in the United States 125 cases of gastric cancer in the Department of Pathology, University of Virginia, and 60 cases of gastric cancer resection in pathology department of the First Affiliated Hospital of Medical University Of Anhui, 185 cases were made of 2 gastric carcinoma tissue chips respectively, and the expression of CD44v6 and FOXD3 was examined with immunohistochemical method (Envision two step method). The relationship between the clinicopathological parameters of the two patients with gastric cancer and the correlation between the two were analyzed and compared with the results of the first part. Results: the first part, the expression in the traditional pathological sections: (1) the positive expression rate of CD44v6 protein in gastric carcinoma was 88% (88/100), obviously higher than that in the normal gastric mucosa adjacent to the cancer group. The positive rate of 22.5% (9/40) was significant (x 2=57.601, P0.001). The expression level of CD44v6 in gastric cancer tissues was significantly correlated with the degree of differentiation of gastric cancer, depth of invasion, lymph node metastasis, and clinical TNM stage (P0.05). There was no correlation with sex, age and tumor diameter of the patients (P0.05); (2) FOXD3 protein. The positive expression rate of 22% (22/100) in gastric carcinoma was significantly lower than that in normal gastric mucosa by 90% (36/40), and the difference was statistically significant (x 2=49.694, P0.001). The expression level of FOXD3 protein in gastric cancer tissues was significantly associated with the degree of differentiation of gastric cancer, depth of infiltration, lymph node metastasis, and clinical TNM staging. Correlation (P0.05) was not related to the sex, age and tumor diameter of the patients (P0.05); (3) the expression of CD44v6 protein and FOXD3 protein was significantly negatively correlated (rs=-0.276, P0.01) in gastric cancer tissues. The second part, expression in the tissue microarray: (1) the positive rate of CD44v6 protein in gastric cancer tissues was 47.27% (52/110), significantly higher than that in cancer. The positive expression rate of para normal tissue was 22.5% (9/40), which had significant statistical difference (x 2=7.461, P0.01). The expression level of CD44v6 in gastric cancer tissues was significantly correlated with the depth of gastric cancer, lymph node metastasis, and clinical TNM stage (P0.05). There was no correlation with sex, age, tumor diameter and differentiation degree of the patients (P0.05). In addition to the difference in the degree of differentiation, the results were consistent with the results of the first part. (2) the positive rate of FOXD3 protein in gastric cancer tissues was 30.91% (34/110), which was significantly lower than that of FOXD3 protein in normal gastric mucosa by 90% (36/40). The difference was significant (x 2=36.747, P0.001), and the expression of FOXD3 in gastric cancer tissues was expressed. There was a significant correlation between the level of gastric cancer, lymph node metastasis, and clinical TNM staging (P0.05). There was no correlation with sex, age, tumor diameter and differentiation of the patients (P0.05). In addition to differentiation, the results were consistent with the first part of the results; (3) the expression of CD44v6 protein and FOXD3 protein in gastric cancer tissue Significant negative correlation (rs=-0.583, P0.001). Conclusion: (1) CD44v6 is a marker of cancer stem cell tumor markers, which is closely related to biological behavior such as tumor invasion, metastasis and prognosis. (2) FOXD3 is a key transcription factor of stem cells, which is closely related to biological behavior such as tumor invasion, transfer and prognosis. (3) CD44v6 and FOXD3 The expression of protein has a significant negative correlation. Both in the development and invasion of gastric cancer may be a mutually restricted.FOXD3 may also be a marker of cancer stem cell tumor markers. (4) tissue chip is a high throughput, efficient detection of clinical tissue samples, compared with the traditional slice specimens with rapid, economical, time-saving and labor-saving characteristics.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.2

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