FOLFOX化疗结直肠癌患者CHRDL1基因表达特征及作用机制的生物信息学分析  

Bioinformatics analysis of CHRDL1 gene expression and mechanism of FOLFOX chemotherapy in colorectal cancer

作　　者：黄丹丹 陶勇 HUANG Dandan;TAO Yong(Department of Anorectal Surgery,Hangzhou Third People's Hospital,Hangzhou 310009,China;不详)

机构地区：[1]杭州市第三人民医院肛肠外科,310009 [2]宁波大学附属第一医院结直肠肛门外科

出　　处：《浙江医学》2023年第6期594-598,I0005,I0006,共7页Zhejiang Medical Journal

基　　金：杭州市卫生科技计划项目(A20200024)。

摘　　要：目的 探讨FOLFOX化疗结直肠癌(CRC)患者CHRDL1基因表达特征及作用机制。方法 利用基因表达汇编数据库下载化疗方案为FOLFOX的CRC患者的基因表达芯片数据集GSE69657,应用R软件筛选出差异基因。利用京都基因和基因组百科全书的基因集分析差异基因可能参与的信号通路,构建蛋白互作网络(PPI),分析差异基因与免疫检查点基因、免疫浸润细胞的关系。结果 分析获得以FOLFOX化疗为基础的CRC患者的差异基因86个,包括表达上调基因62个和表达下调基因24个,其中表达上调基因CHRDL1差异显著。不同肿瘤分期、肿瘤分化程度、淋巴结转移、TP53突变状态的CRC患者CHRDL1基因表达水平比较,差异均有统计学意义(均P<0.05)。CHRDL1基因可能参与的信号通路有11个,主要包括剪接体、磷酸化、切除修复、同源重组、RNA聚合酶、核苷酸切除修复、细胞周期、嘧啶代谢、DNA复制、错配修复、嘌呤代谢等。PPI显示,与CHRDL1基因存在直接互作关系的关键基因有RGMA、HFE2、NOG、BMP7、CHRD等,差异均有统计学意义(均P<0.05)。CHRDL1基因与PDCD1、CTLA4、HAVCR2、PDCD1LG2、SIGLEC15、CD274、LAG3、TIGIT等免疫检查点基因关系密切(均P<0.05),且与B细胞、巨噬细胞、自然杀伤细胞等免疫浸润细胞关系密切(均P<0.05)。结论 CHRDL1基因可能是预测奥沙利铂耐药CRC患者的潜在肿瘤标志物,其作用机制可能是通过调节核酸代谢和免疫机制来影响肿瘤细胞耐药。Objective To investigate the expression characteristics and mechanism of CHRDL1 gene in colorectal cancer treated with FOLFOX.Methods The gene expression microarray dataset GSE69657 of colorectal cancer with FOLFOX chemotherapy was downloaded from GEO database,and the differential genes were screened by R software.The signaling pathways of differential genes were analyzed by using the gene set of Kyoto Gene and Genome database,and protein interaction network(PPI)was constructed to analyze the relationship between differential genes,immune checkpoint genes and immune infiltrating cells.Results A total of 86 differential genes in colorectal cancer based on FOLFOX chemotherapy were obtained,including 62 up-regulated genes and 24 down-regulated genes,among which the upregulated gene CHRDL1 was significantly different.There were statistically significant differences in CHRDL1 gene expression between colorectal cancer patients with different tumor stages,tumor differentiation,lymph node metastasis,and TP53 mutation status(all P<0.05).There are 11 signaling pathways that CHRDL1 gene may participate in,including spliceosome,pentose phosphate pathway,base excision repair,homologous recombination,RNA polymerase,nucleotide excision repair,cell cycle,pyrimidine,metabolism,DNA replication,mismatch repair,purine metabolism.PPI showed that the key genes directly interacting with CHRDL1 gene were RGMA,HFE2,NOG,BMP7,CHRD,etc.,and the differences were statistically significant(all P<0.05).CHRDL1 gene was closely related to PDCD1,CTLA4,HAVCR2,PDCD1LG2,SIGLEC15,CD274,LAG3,TIGIT and other immune checkpoint genes(all P<0.05).It was closely related to immune infiltrating cells such as B cells,macrophages and natural killer cells(all P<0.05).Conclusion CHRDL1 gene may be a potential tumor marker for predicting oxaliplatin resistance,and its mechanism may affect the drug resistance of tumor cells by regulating nucleic acid metabolism and immune mechanism.

关 键 词：FOLFOX 结直肠癌 CHRDL1基因 作用机制 

分 类 号：R735.34[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]