剪接因子SF2/ASF在胰腺癌中的表达及其临床意义

doi:10.3969/j.issn.1004-616x.2023.03.009

摘要/Abstract

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。

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

Abstract: 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 P53 and Ki67. Our findings suggest that SF2/ASF can serve as a new target for pancreatic cancer diagnosis and treatment.

Key words: cancerous pancreatic, splicing factor 2/alternative splicing factor, mutant P53, Ki67, immunohistochemistry

中图分类号:

R735.9

孟琳, 杨华宇, 马秀梅. 剪接因子SF2/ASF在胰腺癌中的表达及其临床意义[J]. 癌变·畸变·突变, 2023, 35(3): 209-214.

MENG Lin, YANG Huayu, MA Xiumei. Expression of the splicing factor SF2/ASF in pancreatic cancer tissues and its relationship with clinicopathological features[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(3): 209-214.

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