摘要
目的:探讨Fer/Cip4同源性(Fer/Cip4 homology,FCH)和双Src同源性3(Src homology 3,SH3)结构域2(FCH and double SH3 domains 2,FCHSD2)在肺鳞状细胞癌(squamous cell lung cancer,LUSC)中的表达情况,并分析其与患者预后的关系。方法:采用肿瘤免疫评估资源2(Tumor Immune Estimation Resource 2,TIMER2)进行泛癌分析,发现FCHSD2的表达差异。用Kaplan-Meier绘图仪评估FCHSD2对LUSC的预后价值,使用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据进行确认。并通过定量RT-PCR检测4种NSCLC细胞系和人支气管上皮样细胞中FCHSD2信使RNA(messenger RNA,mRNA)的表达情况。通过Coexpedia肿瘤数局库分析了FCHSD2共表达的前100个基因,对其功能进行富集分析,并在Sangerbox 3.0平台探究FCHSD2表达与免疫微环境的关系,最终预测FCHSD2的调控微RNA(microRNA,miRNA),并利用RNA相互作用百科全书(Encyclopedia of RNA Interactomes,ENCORI)平台建立LUSC潜在的miRNA-mRNA调控网络。结果:生存分析显示FCHSD2 mRNA水平的降低与LUSC患者OS的降低显著相关。用GO进行功能注释富集分析和KEGG通路富集分析,得到与磷酸转移酶活性、肝素结合等结果相关。且浸润水平随着FCHSD2表达的变化而变化,呈正相关。最终预测出了FCHSD2的调控miRNA,并构建了潜在的miRNA-mRNA调控网络。结论:FCHSD2基因有望成为新型LUSC预后标志物,为LUSC精准治疗策略选择提供重要依据。
Objective:To explore the expression of Fer/Cip4 homology(FCH)and double Src homology 3(SH3)domains 2(FCHSD2)in squamous cell lung cancer(LUSC),and to analyze its relationship with the prognosis of patients.Methods:Tumor Immune Estimation Resource 2(TIMER2)web was used for pan-cancer analysis,and differences in the expression of FCHSD2 were found.The prognostic value of FCHSD2 in LUSC was assessed with a Kaplan-Meier plotter and confirmed using The Cancer Genome Atlas(TCGA)data.The expression of FCHSD2 messenger RNA(mRNA)in nonsmall cell lung cancer(NSCLC)cell lines and human bronchial epithelioid cells was detected by quantitative RT-PCR.The top 100 genes co-expressed by FCHSD2 were analyzed through the Coexpedia tumor database.And their function was analyzed by enrichment analysis,and the relationship between FCHSD2 expression and immune microenvironment were explored on the Sangerbox 3.0 platform.Finally,by predicting the regulatory microRNA(miRNA)of FCHSD2,and using the Encyclopedia of RNA Interactomes(ENCORI)platform,a potential regulatory network of miRNA mRNA of LUSC was established.Results:Survival analysis showed a significant correlation between a decrease in FCHSD2 mRNA levels and a decrease in OS in LUSC patients.Functional annotation enrichment analysis and KEGG pathway enrichment analysis were conducted using GO,and results related to phosphotransferase activity and heparin binding were obtained.And the infiltration level changes with the expression of FCHSD2,showing a positive correlation.Finally,the regulatory miRNA of FCHSD2 was predicted and a potential miRNA mRNA regulatory network was constructed.Conclusion:FCHSD2 gene is expected to become a new type of LUSC prognostic marker,which provides an important basis for the selection of precise treatment strategies for LUSC.
作者
蒋代顺
张璐
刘义
JIANG Daishun;ZHANG Lu;LIU Yi(School of Pharmacy,Guangdong Medical University(Zhanjiang Campus),Zhanjiang Guangdong 524000;Guangdong Natural Medicine Research and Development Laboratory,Guangdong Medical University,Zhanjiang Guangdong 524000,China)
出处
《临床与病理杂志》
CAS
2023年第6期1074-1085,共12页
Journal of Clinical and Pathological Research
基金
国家自然科学基金(82073054)。