剪接因子SF2/ASF在胰腺癌中的表达及其临床意义  

Expression of the splicing factor SF2/ASF in pancreatic cancer tissues and its relationship with clinicopathological features

作　　者：孟琳 杨华宇[1] 马秀梅[1,2] MENG Lin;YANG Huayu;MA Xiumei(Inner Mongolia Medical University,Hohhot 010110;Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia,China)

机构地区：[1]内蒙古医科大学,内蒙古呼和浩特010110 [2]内蒙古医科大学附属医院,内蒙古呼和浩特010050

出　　处：《癌变．畸变．突变》2023年第3期209-214,共6页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：内蒙古自治区自然科学基金(2018MS08021)。

摘　　要：目的:探讨胰腺癌组织中剪接因子2/选择性剪接因子(SF2/ASF)的表达,及其与抑癌基因P53(突变型)、增殖标志物Ki67和患者临床病理指标之间的相关性。方法:采用GEPIA数据库分析350例胰腺癌组织和癌旁正常组织中SRSF1基因(SF2/ASF的编码基因)的表达差异,以及SRSF1与TP53和MKi67(Ki67的编码基因)的相关性;采用免疫组织化学法检测60例胰腺癌组织及对应的癌旁正常组织中SF2/ASF、突变型P53和Ki67蛋白的表达,采用Pearson相关性分析研究SF2/ASF与突变型P53和Ki67的相关性,以及SF2/AFS蛋白表达水平与胰腺癌患者临床病理学指标的关系;采用Cox比例风险回归模型进行预后分析。结果:GEPIA数据库分析结果表明,与癌旁正常组织相比,SRSF1基因在胰腺癌组织中的表达水平显著升高(P<0.01),SRSF1与TP53和MKi67的表达水平均相关(r分别为0.28和0.32,均为P<0.01);免疫组化检测结果显示,与癌旁正常组织相比,SF2/ASF蛋白、突变型P53和Ki67蛋白在胰腺癌组织中的表达水平显著升高(P<0.01)。Pearson相关性分析结果表明胰腺癌组织中,SF2/ASF蛋白表达水平与突变型P53蛋白及Ki67增殖指数有关(r分别为-0.386和0.275,均为P<0.05)。卡方检验结果表明SF2/ASF在胰腺癌中的表达水平与胰腺癌分化程度、淋巴结转移情况以及有无远端脏器转移有关(均为P<0.01),与胰腺癌发生部位和TNM分期无明显相关(P>0.05)。Cox风险回归分析表明,SF2/ASF高表达和患者年龄是影响患者总生存期的独立危险因素(均为P<0.01)。结论:SF2/ASF、突变型P53和Ki67蛋白在胰腺癌中高表达,且SF2/ASF的表达与突变型P53和Ki67具有相关性,提示SF2/ASF有望成为胰腺癌诊治的新靶点。OBJECTIVE:To investigate expression of the splicing factor 2/alternative splicing factor(SF2/ASF)in pancreatic cancer tissues and its correlation with oncogene P53(mutant type),proliferation marker Ki67 and clinicopathological features.METHODS:Differences in expression of the SRSF1 gene(the gene encoding SF2/ASF)in 350 pancreatic cancer tissues and normal tissues adjacent to the cancer were evaluated based on GEPIA database analysis;and correlations with SRSF1 and TP53 and MKi67 were analyzed.In addition,expression of SF2/ASF,mutant P53 and Ki67 protein in 60 pancreatic cancer tissues and corresponding normal tissues were evaluated,as well as correlations between SF2/ASF and mutant P53 and Ki67 using Pearson correlation analysis,and correlations between SF2/AFS protein expression levels and clinicopathological indices of pancreatic cancer patients,and prognostic analysis using Cox proportional risk regression model.RESULTS:Results from our database analysis show that expression of the SRSF1 gene was significantly higher in pancreatic cancer tissues compared with normal tissues(P<0.01),and expression of the SRSF1 was correlated with both TP53 and MKi67(r=0.28 and 0.32,respectively,both P<0.01).Results from the immunohistochemical assay and the Pearson correlation analysis show that SF2/ASF was correlated with mutant P53 protein and Ki67 proliferation index(r=-0.386 and 0.275,respectively,P<0.05)in pancreatic cancer tissues.The chi-square test show that expression of the SF2/ASF in pancreatic cancer was correlated with the degree of pancreatic cancer differentiation(P<0.01),whether with lymph node metastasis(P<0.01)and the presence of distal organ metastasis(P<0.01),but not with the site of pancreatic cancer occurrence and TNM stage(P>0.05).Cox risk regression analysis show that high expression of SF2/ASF and patient age(both P<0.01)were independent risk factors for overall patient survival.CONCLUSION:SF2/ASF,mutant P53 and Ki67 proteins were highly expressed in pancreatic cancer,and SF2/ASF correlates with mutant

关 键 词：胰腺癌 剪接因子2/选择性剪接因子 突变型P53 KI67 免疫组织化学 

分 类 号：R735.9[医药卫生—肿瘤]