【作者】 蒋敏；

【导师】 杨小丽；

【作者基本信息】 广西医科大学 ， 生物医学工程， 2020， 硕士

【摘要】 目的:利用GEO公共数据库研究分析人口腔鳞状细胞癌组织及口腔正常组织中CDC5L m RNA的表达特征;检测口腔鳞状细胞癌患者的癌组织及癌旁粘膜组织中CDC5L蛋白的表达;探讨口腔鳞状细胞癌组织中CDC5L的表达与口腔鳞状细胞癌的发生发展的关系。方法:1.从GEO公共数据库(https://www.Ncbi.nlm.nih.gov/gds)下载口腔鳞状细胞癌的相关芯片,分析纳入芯片中的口腔鳞状细胞癌组织和口腔正常组织中CDC5L m RNA的表达差异;绘制ROC曲线,探讨CDC5L在口腔鳞状细胞癌中的诊断意义;提取芯片中口腔鳞状细胞癌患者的临床信息,分析CDC5L的表达与临床资料的关系。2.应用Stata软件将纳入芯片的数据进行荟萃分析,分析口腔鳞状细胞癌组织和正常组织中CDC5L m RNA的表达差异;将包含来自不同大洲和国家病例的芯片数据进行亚组分析;采用Begg秩相关检验和Egger线性回归分析法分析芯片的发表偏倚程度;采用敏感性分析评估研究结果的稳定性。3.从病理科收集口腔鳞状细胞癌组织及对应癌旁粘膜组织,并且收集患者的临床资料:民族、年龄、性别、血型、吸烟、饮酒、肿瘤大小、肿瘤部位、TNM分期、淋巴结转移、分化程度;4.采用免疫组织化学染色法检测CDC5L蛋白在口腔鳞状细胞癌组织和癌旁粘膜组织中的分布和表达情况;5.分析口腔鳞状细胞癌组织中CDC5L的表达与患者临床分期的关系。结果:1.从GEO数据库中筛选出16个芯片,其中的4个芯片的口腔鳞状细胞癌组织中CDC5L m RNA的表达量比正常组织高,并且差异有统计学意义(P<0.05)。其余12个芯片的癌组织与正常组织中的CDC5L m RNA表达无统计学差异(P>0.05)。在4个有表达差异的芯片中,其中3个芯片数据的ROC曲线图下面积AUC均大于0.7(P<0.005)。CDC5L的表达与患者的年龄和性别无关(P>0.05)。2.纳入芯片的荟萃分析结果显示,口腔鳞状细胞癌组织中CDC5L m RNA的表达高于正常组织,并且差异有统计学意义(P<0.05)。北美洲和亚洲人群的OSCC组织中CDC5L m RNA的表达高于正常组织(P<0.05)。美国人和中国人的OSCC组织中CDC5L m RNA的表达高于正常组织(P<0.05)。纳入的芯片无明显的发表偏倚,研究结果具有良好的稳定性。3.免疫组织化学染色结果显示,CDC5L蛋白的主要在细胞核中表达。口腔鳞状细胞癌患者的癌组织中CDC5L蛋白的表达高于癌旁粘膜组织,并且差异有统计学意义(P<0.05)。4.口腔鳞状细胞癌分期为Ⅰ～Ⅱ期患者的癌组织中CDC5L的表达比Ⅲ～Ⅳ期患者的高,并且差异有统计学意义(P<0.05);而CDC5L的表达与民族、年龄、性别、血型、吸烟、饮酒、肿瘤大小、肿瘤部位、淋巴结转移、分化程度无关(P>0.05)。结论:口腔鳞状细胞癌组织中CDC5L m RNA的表达明显高于口腔正常组织;口腔鳞状细胞癌组织中CDC5L蛋白的表达明显高于癌旁粘膜组织,CDC5L的表达可能与口腔鳞状细胞癌的发生发展有关。更多还原

【Abstract】 Objective: We used the GEO public database to study and analyze the expression characteristics of CDC5 L m RNA in human oral squamous cell carcinoma tissues and oral normal tissues.Then we detected the expression of CDC5 L protein in cancer tissues and adjacent mucosal tissues of patients with oral squamous cell carcinoma,and explored the relationship between the expression of CDC5 L in oral squamous cell carcinoma and the occurrence and development of oral squamous cell carcinoma.Methods: 1.We searched and downloaded the related gene chips of oral squamous cell carcinoma from GEO public database(https://www.Ncbi.nlm.nih.gov/gds).And we analyzed the difference of CDC5 L expression in tumor tissues of oral squamous cell carcinoma and oral normal tissues.Then we drew ROC curve.The area under the ROC curve in the diagnosis was used to explore the diagnostic significance of CDC5 L in oral squamous cell carcinoma.The basic information of patients with oral squamous cell carcinoma in the chips was extracted to analyze the relationship between the expression of CDC5 L and the basic information of patients.2.We performed a meta-analysis of all the data included in gene chips.Then we analyzed the difference of CDC5 L expression in oral squamous cell carcinoma and normal tissues.Subgroup analysis of chips containing oral squamous cell carcinoma and normal tissues from different continents and countries were performed.The publication bias was detected by Begg’s test and Egger’s test.The stability of the study was assessed by sensitivity analysis;3.The oral squamous cell carcinoma tissues and corresponding adjacent tissues were collected from hospital pathology.And clinical information of patients were also collected,containing ethnicity,age,gender,blood type,smoking,drinking,tumor size,tumor location,TNM classification staging,lymph node metastasis,degree of differentiation.4.Immunohistochemical staining was used to detect the distribution and expression of CDC5 L in tumor tissues and adjacent mucosa tissues;5.We analyzed the relationship between the expression of CDC5 L in oral squamous cell carcinoma and the clinical stage.Results: 1.We selected 16 gene chips from the GEO database.we found that the difference expression of CDC5 L m RNA in oral squamous cell carcinoma tissues and oral normal tissues in four chips was statistically significant(P<0.05).But in other 12 chips,there was no statistically significant difference in the expression of CDC5 L mRNA in oral squamous cell carcinoma tissues and normal tissues(P>0.05).Three of these four chips with different expressions showed that the area under the ROC curve were greater than 0.7(P<0.05).The expression of CDC5 L was not related to the patient’s age and gender(P>0.05).2.The results of meta-analysis showed that the difference expression of CDC5 L in tumor tissues and normal tissues in sixteen chips was statistically significant(P<0.05).The expression of CDC5 L in OSCC tissues of North American and Asian populations was higher than that of normal control tissues(P<0.05).And the expression of CDC5 L in OSCC tissues of Americans and Chinese was higher than that of normal control tissues(P<0.05).Begg’s test and Egger’s test showed there was no obvious publication bias in the meta-analyses.The sensitivity analysis showed the meta-analyses was robust.3.Immunohistochemical staining showed that CDC5 L protein was mainly expressed in the nucleus.The expression of CDC5 L in tumor tissues of patients with oral squamous cell carcinoma was higher than that of adjacent tissues,and the difference was statistically significant(P <0.05).4.The expression of CDC5 L in tumor tissues of oral squamous cell carcinoma with stage Ⅰ～Ⅱ was higher than that of stage Ⅲ～Ⅳ(P<0.05).The expression of CDC5 L was not related to the patient’s ethnicity,age,gender,blood type,smoking,drinking,tumor size,tumor location,lymph node metastasis,degree of differentiation(P>0.05).Conclusion: The expression of CDC5 L mRNA in oral squamous cell carcinoma tissue is significantly higher than that in oral normal tissues.And the expression of CDC5 L protein in oral squamous cell carcinoma tissue is also significantly higher than that of paracancerous mucosa tissue.The expression of CDC5 L may be related to the occurrence and development of oral squamous cell carcinoma.更多还原