FOXL2NB在结直肠癌中的表达和临床意义  

Expression and clinical significance of FOXL2NB in colorectal cancer

作　　者：杜风 陈翌阳[2] 张楠[1] 徐俊玄 宁婷婷 朱圣韬[1] 张澍田[1] DU Feng;CHEN Yiyang;ZHANG Nan;XU Junxuan;NING Tingting;ZHU Shengtao;ZHANG Shutian(Department of Gastroenterology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China;Department of Laboratory Medicine,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院消化内科,北京100050 [2]首都医科大学附属北京友谊医院检验科,北京100050

出　　处：《基础医学与临床》2023年第6期909-915,共7页Basic and Clinical Medicine

基　　金：国家自然科学基金(82203700);中国博士后科学基金(2022M720100);博士后创新人才支持计划(BX20220216);首都医科大学附属北京友谊医院“友谊种子计划”人才项目(YYZZ202216)。

摘　　要：目的分析叉头框L2旁基因(FOXL2NB)在结直肠癌(CRC)中的表达及临床意义,探讨FOXL2NB对CRC细胞的作用。方法RT-qPCR和蛋白免疫印迹分析CRC组织和细胞中FOXL2NB的表达;Transwell和CCK-8实验探讨FOXL2NB在SW620细胞增殖和迁移的作用;Kaplan-Meier法和多因素Cox回归分析评估FOXL2NB对CRC预后的影响;基因集富集分析比较高、低风险组间分子信号通路差异,CIBERSORT R包计算CRC组织中FOXL2NB表达与免疫细胞浸润的关系,limma R包计算与FOXL2NB表达显著相关的分子。结果FOXL2NB在CRC组织和细胞中的表达水平显著升高(P<0.05);敲低FOXL2NB可抑制CRC细胞的迁移及增殖;高水平的FOXL2NB与CRC患者不良预后相关(P<0.05),可作为CRC预后的独立风险因素(HR=2.27,95%CI=1.78~2.9,P<0.001);FOXL2NB高表达的CRC中细胞黏附分子和肿瘤免疫相关通路被显著富集,CD8+T细胞和活化树突状细胞显著增多,M0巨噬细胞显著减少。FOXL2NB基因表达与SCRT2、MGAT5B、SELENOV、FOXB1、KCNA4、LRRC14B和SLC32A1基因表达正相关。结论FOXL2NB在CRC中高表达,可能预示CRC患者不良预后。FOXL2NB可能促进结直肠癌细胞增殖和迁移。Objective To analyze the forkhead box L2 neighbor(FOXL2NB)expression in colorectal cancer(CRC)and its potential clinical significance,and to explore the role of FOXL2NB in CRC cells.Methods Real time qPCR and Western blot were used to analyze the expression of FOXL2NB in CRC tissues and cells.Transwell and CCK-8 assay were used to investigate the effect of FOXL2NB on the proliferation and migration in SW620 cell line.Kaplan-Meier and multivariate Cox regression analysis were used to evaluate the prognostic significance of FOXL2NB in CRC patients.CIBERSORT R package was used to calculate the correlation between FOXL2NB expression and immune cell infiltration in CRC tissues.limma R package was used to calculate the genes that significantly correlated with FOXL2NB expression.Results The mRNA and protein levels of FOXL2NB were significantly increased in CRC cell lines and tissues(P<0.05).High level of FOXL2NB was associated with shorter overall survival and progression free survival in CRC patients(P<0.05),which could be used as an independent risk factor for CRC prognosis(HR=2.27,95%CI=1.78-2.9,P<0.001).FOXL2NB knockdown inhibited the migration and proliferation of CRC cells.Cell adhesion molecules and tumor immune-related pathways were significantly enriched in CRC with high FOXL2NB expression,CD8+T cells and activated dendritic cells were significantly increased,while M0 macrophages were significantly decreased.FOXL2NB expression was positively correlated with SCRT2,MGAT5B,SELENOV,FOXB1,KCNA4,LRRC14B and SLC32A1 genes.Conclusions FOXL2NB is highly expressed in CRC and potentially predicts poor prognosis.FOXL2NB might promote CRC cell proliferation and migration.

关 键 词：结直肠癌 叉头框转录因子 FOXL2NB 细胞黏附 肿瘤免疫 

分 类 号：R735.7[医药卫生—肿瘤]