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  本文選題：CD44v6 + FOXD3��； 參考：《安徽醫(yī)科大學》2015年碩士論文

【摘要】：目的:研究腫瘤干細胞標志物CD44v6和干細胞關(guān)鍵轉(zhuǎn)錄因子FOXD3蛋白在胃癌及其癌旁正常組織中的表達,分析兩者與胃癌患者臨床病理參數(shù)間的關(guān)系,探討兩種蛋白與胃癌浸潤、轉(zhuǎn)移以及預后等生物學行為的關(guān)系;通過研究腫瘤干細胞標志物CD44v6在胃癌組織中的表達情況,以及對FOXD3與CD44v6蛋白表達的相關(guān)性的統(tǒng)計分析,探討FOXD3作為胃癌干細胞標志物的可能性。方法:第一部分:收集胃癌手術(shù)切除標本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(包括粘液細胞癌、粘液腺癌)和癌旁正常胃黏膜組織40例,結(jié)合免疫組織化學方法(Envision二步法)對CD44v6和FOXD3蛋白的表達進行檢測,對兩者與胃癌臨床病理參數(shù)間的關(guān)系進行統(tǒng)計分析,并且分析兩者之間的相關(guān)性。第二部分:選取1982-2002年美國弗吉尼亞大學醫(yī)學院病理系胃癌存檔病例125例,以及安徽醫(yī)科大學第一附屬醫(yī)院病理科胃癌切除手術(shù)標本60例,共185例,將上述兩組胃癌標本分別制成2張胃癌組織芯片,結(jié)合免疫組織化學方法(Envision二步法)對CD44v6和FOXD3的表達進行檢測,分析兩者與胃癌患者臨床病理參數(shù)間的關(guān)系以及兩者之間的相關(guān)性,并且與第一部分結(jié)果進行對比。結(jié)果:第一部分、在傳統(tǒng)病理切片標本中的表達:(1)CD44v6蛋白在胃癌組織的陽性表達率為88%(88/100),明顯高于其在癌旁正常胃黏膜組織的陽性率22.5%(9/40),差異具有顯著統(tǒng)計學意義(χ2=57.601,P0.001);CD44v6在胃癌組織中的表達水平與胃癌的分化程度、浸潤深度、淋巴結(jié)轉(zhuǎn)移、臨床TNM分期具有明顯相關(guān)性(P0.05),與患者的性別、年齡以及腫瘤直徑均無相關(guān)性(P0.05);(2)FOXD3蛋白在胃癌組織的陽性表達率為22%(22/100)明顯低于其在癌旁正常胃黏膜組織中陽性表達率90%(36/40),差異具有顯著統(tǒng)計學意義(χ2=49.694,P0.001);FOXD3蛋白在胃癌組織中的表達水平與胃癌的分化程度、浸潤深度、淋巴結(jié)轉(zhuǎn)移、臨床TNM分期具有明顯相關(guān)性(P0.05),與患者的性別、年齡以及腫瘤直徑均無相關(guān)性(P0.05);(3)在胃癌組織中,CD44v6蛋白和FOXD3蛋白的表達呈顯著負相關(guān)(rs=-0.276,P0.01)。第二部分、在組織芯片中的表達:(1)CD44v6蛋白在胃癌組織中陽性率為47.27%(52/110),明顯高于其在癌旁正常組織的陽性表達率22.5%(9/40),兩者具有明顯統(tǒng)計學差異(χ2=7.461,P0.01);CD44v6在胃癌組織中的表達水平與胃癌的浸潤深度、淋巴結(jié)轉(zhuǎn)移、臨床TNM分期具有明顯相關(guān)性(P0.05),與患者的性別、年齡、腫瘤直徑以及分化程度均無相關(guān)性(P0.05);除分化程度方面的差異外,此結(jié)果與第一部分結(jié)果一致。(2)FOXD3蛋白在胃癌組織中陽性率為30.91%(34/110),明顯低于FOXD3蛋白在癌旁正常胃黏膜組織中的陽性表達率90.0%(36/40),差異有顯著統(tǒng)計學意義(χ2=36.747,P0.001);FOXD3在胃癌組織中的表達水平與胃癌的浸潤深度、淋巴結(jié)轉(zhuǎn)移、臨床TNM分期具有明顯相關(guān)性(P0.05),與患者的性別、年齡、腫瘤直徑以及分化程度均無相關(guān)性(P0.05);除分化程度方面的差異外,此結(jié)果與第一部分結(jié)果一致;(3)在胃癌組織中,CD44v6蛋白和FOXD3蛋白的表達呈顯著負相關(guān)(rs=-0.583,P0.001)。結(jié)論:(1)CD44v6作為胃癌干細胞腫瘤標記物,其與腫瘤的浸潤、轉(zhuǎn)移以及預后等生物學行為的關(guān)系密切。(2)FOXD3作為干細胞關(guān)鍵轉(zhuǎn)錄因子,其與腫瘤的浸潤、轉(zhuǎn)移以及預后等生物學行為的關(guān)系密切。(3)CD44v6與FOXD3蛋白的表達呈顯著負相關(guān),兩者在胃癌的發(fā)生發(fā)展和侵襲轉(zhuǎn)移中可能是相互制約的。FOXD3可能也為胃癌干細胞腫瘤標記物。(4)組織芯片為高通量、高效檢測的臨床組織樣本,與傳統(tǒng)切片標本相比具有快速、經(jīng)濟、省時、省力的特點。
[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.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R735.2

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本文編號：2084903