基于生物信息学数据探究PKIG与肺鳞癌的相关性及其在肿瘤微环境中的作用

Exploration of the Perturbation of PKIG in Lung Squamous Cell Carcinoma and the Role in Tumor Microenvironment Based on Bioinformatics Method

背景与目的肺癌是全球癌症相关死亡的主要原因,患者从手术、放疗和化疗这些传统治疗方法中生存获益有限。免疫疗法作为肺癌的一种新兴治疗手段,显著延长了患者的总生存期(overall survival,OS),然而,仅有一部分患者能够从中获益,需要我们更深入地探索免疫治疗生物标志物以筛选优势人群。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)和基因表达综合数据库(Gene Expression Omnibus,GEO)下载原始数据,利用R软件和TIMER数据库筛选肺鳞癌(lung squamous cell carcinoma,LUSC)免疫预后相关基因。在TCGA和GEO数据库中研究了目标基因的表达情况,并通过R软件和TISIDB数据库对目标基因进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析以及与肿瘤免疫特征之间的相关性分析。结果我们筛选出cAMP依赖性蛋白激酶抑制剂γ(protein kinase inhibitor gamma,PKIG)这个免疫预后相关基因,PKIG在LUSC和正常组织中的表达有明显差异,并对LUSC的诊断和预后评估具有重要参考价值。PKIG差异基因主要集中富集在体液免疫反应的调节等过程。PKIG的表达与调节性T细胞(regulatory T cells,Tregs)的浸润水平呈正相关(r=0.340,P<0.001)。此外,PKIG还与LUSC中趋化因子配体2(chemokine C-C motifligand 2,CCL2)(r=0.503,P<0.001)、CXC趋化因子配体12(CXC chemokine ligand 12,CXCL12)(r=0.386,P<0.001)和CXC趋化因子受体4(CXC-chemokine receptor 4,CXCR4)(r=0.492,P<0.00l)等趋化因子/趋化因子受体以及细胞程序性死亡蛋白1(programmed cell death protein 1,PDCD1)(r=0.359,P<0.001)、细胞毒性T淋巴细胞相关蛋白4(cytotoxic T-lymphocyte associated antigen 4,CTLA4)(r=0.375,P<0.001)和T细胞免疫球蛋白ITIM结构域(T cell immunoglobulin and ITIM domains,TIGIT)(r=0.305,P<0.001)等免疫抑制剂的表达水平呈正相关。结论通过生物信息学分析筛选出LUSC免疫预后相关基因PKIG,PKIG与LUSC预后和免疫微环境高度相关,有望成为LUSC免疫治疗的潜在生物分子标志物。

Background and objective Lung cancer is the leading cause of cancer-related death worldwide,and patients have limited survival benefits from traditional treatments such as surgery,radiotherapy and chemotherapy.As a new treatment for lung cancer,immunotherapy has significantly prolonged the overall survival(OS)of patients.However,only some patients can benefit from it.We need to explore immunotherapy biomarkers more deeply to screen for advantages.Methods The original data were downloaded from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)database,and the immunological and prognostic genes of lung squamous cell carcinoma(LUSC)were screened using R software and TIMER database.The expression of target genes was studied in TCGA and GEO databases,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and correlation analysis with tumor immune characteristics were performed by R software and TISIDB database.Results We screened out a gene related to immunity and prognosis,cAMP dependent protein kinase inhibitor γ(PKIG),which is significantly differentially expressed in LUSC and normal tissues,and has important reference value for the diagnosis and prognosis assessment of LUSC.PKIG differential genes are mainly concentrated in the regulation of humoral immune response and other processes.The expression of PKIG was positively correlated with the infiltration level of regulatory T cells(Tregs)(r=0.340,P<0.001).In addition,the expression level of PKIG was positively correlated with the expression of chemokines/chemokine receptors such as chemokine C-C motif ligand 2(CCL2)(r=0.503,P<0.001),CXC chemokine ligand 12(CXCL12)(r=0.386,P<0.001)and CXC-chemokine receptor 4(CXCR4)(r=0.492,P<0.001),and immunoinhibitors such as programmed cell death protein 1(PDCD1)(r=0.359,P<0.001),cytotoxic T-lymphocyte associated antigen 4(CTLA4)(r=0.375,P<0.001)and T cell immunoglobulin and ITIM domains(TIGIT)(r=0.305,P<0.001)in LUSC.Conclusion The immunological and prognostic gene PKIG in lung squamous cell carcinoma was screened through bioinformatics analysis.PKIG is highly correlated with LUSC prognosis and immune microenvironment,and is expected to be a potential biomolecular marker for LUSC immunotherapy.