【作者】 李浩；

【导师】 朱新国；

【作者基本信息】 苏州大学 ， 外科学（普通外科学）（专业学位）， 2021， 硕士

【摘要】 目的:结直肠癌目前是中国最常见的消化道恶性肿瘤之一,它的年发病率排在恶性肿瘤的第三位。FGF1(成纤维细胞生长因子1)是由FGF家族成员FGF1基因编码产生的细胞因子,近年研究认为其与多种肿瘤密切相关,本研究意在探究FGF1在结直肠癌中的表达情况,以及FGF1在结直肠癌发生发展中所发挥的作用,以期发现新的治疗结直肠癌的生物标志物。方法:运用免疫组化染色和实时荧光定量PCR检测FGF1在结直肠癌组织和癌旁组织中的表达。Western Blotting检测结直肠癌细胞中FGF1蛋白的表达,运用Transwell、MTT实验和细胞集落形成实验检测结直肠癌细胞增殖和迁移能力。通过生物信息学方法分析TCGA等数据库,预测FGF1在调控结直肠癌细胞增殖迁移通路中的上下信号通路。结果:免疫组化染色和实时荧光定量PCR结果显示FGF1在结直肠癌组织中高表达,且与淋巴结转移和TNM分期存在相关性,FGF1表达阳性的结直肠癌患者术后生存时间明显较阴性患者短,此外FGF1的表达水平是影响结直肠癌患者预后的独立危险因素。细胞实验结果表明FGF1可以促进结直肠癌细胞的增殖和迁移。在结直肠癌中FGF1与AKR1B10密切相关,且FGF1可以介导AKR1B10对结直肠癌细胞增殖和迁移的抑制作用;FGF1可以促进结直肠癌中的EMT过程。结论:FGF1在结直肠癌中异常高表达,且与患者的临床病理特征密切相关,过表达的FGF1显著影响结直肠癌患者的预后;FGF1促进结直肠癌细胞的增殖和迁移。FGF1可以介导AKR1B10对结直肠癌细胞增殖和迁移的抑制作用,FGF1可以通过调控EMT过程进而影响结直肠癌细胞的侵袭迁移。综合结果提示FGF1可以作为结直肠癌诊断和治疗的新靶点。更多还原

【Abstract】 Objective:Colorectal cancer is currently one of the most common gastrointestinal malignancies in China,and its annual incidence ranks third among all malignant tumors.FGF1(fibroblast growth factor 1)is a cytokine produced by the FGF1 gene,a member of the FGF family.Recent studies have shown that it is closely related to a variety of tumors.This study is intended to explore the expression of FGF1 in colorectal cancer and the role of FGF 1 in the occurrence and development of colorectal cancer,with a view to discovering new biomarkers for the treatment of colorectal cancer.Methods:Immunohistochemistry staining and quantitative real-time PCR were used to detect the expression of FGF 1 in colorectal cancer tissues and adjacent tissues.Western Blotting detects the expression of FGF1 protein in colorectal cancer cells,and uses Transwell,MTT experiments and cell colony formation experiments to detect the proliferation and migration ability of colorectal cancer cells.Using bioinformatics methods to analyze TCGA and other databases,predict the up and down signal pathways of FGF 1 in regulating the proliferation and migration pathways of colorectal cancer cells.Results:The results of immunohistochemistry staining and quantitative real-time PCR showed that FGF1 was highly expressed in colorectal cancer tissues,and it was correlated with lymph node metastasis and TNM staging.The survival time of FGF1 positive colorectal cancer patients was significantly shorter than that of negative patients.In addition,the expression level of FGF1 is an independent risk factor affecting the prognosis of patients with colorectal cancer.Cell experiment results show that FGF1 can promote the proliferation and migration of colorectal cancer cells.In colorectal cancer,FGF1 is closely related to AKR1B10,and FGF1 can mediate the inhibitory effect of AKR1B10 on the proliferation and migration of colorectal cancer cells;FGF1 can promote the EMT process in colorectal cancer.Conclusion:FGF1 is abnormally highly expressed in colorectal cancer,and is closely related to the clinicopathological characteristics of patients.The overexpression of FGF1 significantly affects the prognosis of colorectal cancer patients;FGF1 promotes the proliferation and migration of colorectal cancer cell.FGF1 can mediate the inhibitory effect of AKR1B10 on the proliferation and migration of colorectal cancer cells,and FGF1 can affect the invasion and migration of colorectal cancer cell by regulating the EMT process.The comprehensive results suggest that FGF1 can be used as a new target for the diagnosis and treatment of colorectal cancer.更多还原