摘要
目的 基于生物信息学探讨FBXO43在泛癌中的表达及其与免疫细胞浸润和预后的关系.方法 从癌症基因组图谱(TCGA)和基因型-组织表达(GTEx)数据库获取33种癌症的基因表达数据,分析FBXO43在33种癌组织中的表达水平;从TCGA数据库中获得33种癌症的临床病理和生存数据,使用基因表达谱交互式分析(GEPIA)工具分析FBXO43表达与患者临床分期相关性;采用Kaplan-Meier生存分析评估FBXO43表达与预后的关系;利用R语言分析FBXO43与免疫细胞浸润、免疫检查点(ICP)基因、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)、错配修复(MMR)基因的关系.通过基因集富集分析(GSEA)分析FBXO43潜在的生物学机制.采用qRT-PCR检测正常胃黏膜细胞(GES-1)和胃癌细胞(HGC-27、MGC-803、MKN-45),正常肝细胞(LO-2)和肝癌细胞(SMMC-7721、HEPG2、HuH7、MHCC-97H)中FBXO43的表达水平.结果 TCGA联合GTEx数据库统计结果显示,肾上腺皮质癌(ACC)、膀胱尿路上皮癌(BLCA)、乳腺浸润癌(BRCA)、宫颈鳞癌和腺癌(CESC)、胆管癌(CHOL)、结肠癌(COAD)和弥漫性大B细胞淋巴瘤(DLBC)等26种癌组织中,FBXO43的表达均高于正常组织(均P<0.05);而肾嫌色细胞癌(KICH)、睾丸癌(TGCT)和甲状腺癌(THCA)3种癌组织中,FBXO43的表达均低于正常组织(均P<0.05).GEPIA数据分析结果显示,FBXO43表达与ACC、KICH、肾透明细胞癌(KIRC)和肾乳头状细胞癌(KIRP)的临床分期呈正相关,而与卵巢浆液性囊腺癌(OV)和TGCT的临床分期呈负相关(均P<0.05).Kaplan-Meier生存分析结果显示,FBXO43异常表达与多种癌症的预后相关(均P<0.05).其中,FBXO43高表达是ACC、KICH、KIRC、KIRP、脑低级别胶质瘤(LGG)、肝细胞癌(LIHC)、间皮瘤(MESO)和肉瘤(SARC)的危险因素;但在胸腺瘤(THYM)中则是保护因素.XCELL算法发现,FBXO43表达与多形成性胶质细胞瘤(GBM)、KIRP、急性髓系白血病(LAML)、肺鳞状细胞癌(LUSC)和OV等9种癌组织中的免疫评分呈负相关(均P<0.05),并与BLCA、COAD、头颈部鳞癌(HNSC)、SARC和THYM等24种癌组织中的免疫细胞浸润水平密切相关,尤其在SARC中与大部分免疫细胞呈显著负相关(P<0.01).相关性分析表明FBXO43与泛癌中的TMB、MSI和MMR存在显著相关性.GSEA分析显示FBXO43与多种肿瘤的细胞周期和免疫相关功能有关.qRT-PCR结果显示,与正常细胞比较,FBXO43在肝癌细胞中表达上调,在胃癌细胞中表达下降(均P<0.05).结论 FBXO43异常表达与多种癌症的发生、发展密切相关;FBXO43可能是新的免疫细胞浸润和预后的标志物,可为癌症的靶向治疗提供新的方向.
Abstract
Objective To investigate the expression of FBXO43in various cancers and its relationship with immune cell infiltration and prognosis using bioinformatics.Methods Gene expression data for 33 cancers were obtained from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases to analyze FBXO43expression.Clinical and survival data were sourced from the TCGA database.Gene Expression Profiling Interactive Analysis(GEPIA)was used to assess the correlation between FBXO43expression and the clinical stage.Kaplan-Meier survival analysis was used to evaluate the relationship between FBXO43expression and prognosis.R lan-guage was used to analyze the associations between FBXO43expression and clinical stages,immune cell infiltration,immune checkpoint genes,tumor mutation burden(TMB),microsatellite instability(MSI),and mismatch repair(MMR)genes.The potential biological mech-anisms of FBXO43were explored using gene set enrichment analysis(GSEA).Moreover,qRT-PCR was performed to measure FBXO43 expression in normal gastric mucosal cells(GES-1),gastric cancer cells(HGC-27,MGC-803,and MKN-45),normal liver cells(LO-2),and liver cancer cells(SMMC-7721,HEPG2,HuH7,and MHCC97-H).Results Combined TCGA and GTEx database statistics revealed higher FBXO43expression in 26 types of cancer tissues,including adrenocortical carcinoma(ACC),bladder urothelial carcinoma,breast invasive carcinoma,cervical squamous cell carcinoma and endocervical adenocarcinoma,cholangiocarcinoma,colon adenocarcinoma,and diffuse large B-cell lymphoma,than in normal tissues(P<0.05).However,FBXO43expression was lower in three types of cancer tissues:kidney chromophobe(KICH),testicular germ cell tumor(TGCT),and thyroid carcinoma(P<0.05).GEPIA data analysis showed that FBXO43expression positively correlated with the clinical stages of ACC,KICH,kidney renal clear cell carcinoma(KIRC),and kidney renal papillary cell carcinoma(KIRP)and negatively correlated with the clinical stages of ovarian serous cystadenocarcinoma(OV)and TGCT(P<0.05).Kaplan-Meier survival analysis indicated that abnormal FBXO43expression was associated with the prognosis of various cancers(P<0.05).Specifically,high FBXO43expression was a risk factor for ACC,KICH,KIRC,KIRP,low-grade glioma,liver hepato-cellular carcinoma,mesothelioma,and sarcoma,but protective in thymoma(THYM).The XCELL algorithm found that FBXO43expres-sion was negatively correlated with immune scores in nine types of cancer tissues,including glioblastoma multiforme,KIRP,acute myeloid leukemia,lung squamous cell carcinoma,and OV,and closely related to immune cell infiltration levels in 24 types of cancer tissues,espe-cially showing a significant negative correlation with most immune cells in SARC(P<0.01).Correlation analysis revealed a significant association between FBXO43and TMB,MSI,and MMR in all cancers.GSEA analysis indicated that FBXO43is involved in the cell cycle and immune-related functions in various tumors.qRT-PCR results showed that FBXO43expression was upregulated in liver cancer cells and downregulated in gastric cancer cells(all P<0.05).Conclusion Abnormal FBXO43expression is closely associated with the occur-rence and progression of multiple cancers.Thus,FBXO43may serve as a novel marker of immune cell infiltration and prognosis,thereby offering new directions for targeted cancer therapy.
基金项目
甘肃省科技计划创新基地和人才计划(20JR10RA433)
甘肃省科技计划重点研发计划(21YF5WA027)
甘肃省卫生健康行业科研计划(GSWSKY2020-45)
甘肃省教育厅优秀研究生创新之星项目(2022CXZX-746)
国家卫健委胃肠肿瘤诊治重点实验室硕博士/博士后基金项目(NHCDP2022001)
甘肃省人民医院博士研究生导师培育项目(22GSSYA-3)
维普
万方数据