Liu Qing, Li Haitian, Li Bin, Ren Meiyu, Li Zhenqing, Chen Yuzhen, Zheng Zhizhong, Meng Yuqi, Feng Haiming
Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, China.
Zhongguo Fei Ai Za Zhi. 2023 Jul 20;26(7):523-537. doi: 10.3779/j.issn.1009-3419.2023.102.24.
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.
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.
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.
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.
肺癌是全球癌症相关死亡的主要原因,患者从手术、放疗和化疗等传统治疗中获得的生存益处有限。作为肺癌的一种新治疗方法,免疫疗法显著延长了患者的总生存期(OS)。然而,只有部分患者能从中获益。我们需要更深入地探索免疫疗法生物标志物以筛选出优势人群。
原始数据从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)下载,使用R软件和TIMER数据库筛选肺鳞状细胞癌(LUSC)的免疫和预后基因。在TCGA和GEO数据库中研究目标基因的表达,并通过R软件和TISIDB数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析以及与肿瘤免疫特征的相关性分析。
我们筛选出一个与免疫和预后相关的基因,环磷酸腺苷依赖性蛋白激酶抑制剂γ(PKIG),其在LUSC和正常组织中显著差异表达,对LUSC的诊断和预后评估具有重要参考价值。PKIG差异基因主要集中在体液免疫反应调控等过程。PKIG的表达与调节性T细胞(Tregs)的浸润水平呈正相关(r = 0.340,P < 0.001)。此外,PKIG的表达水平与LUSC中趋化因子/趋化因子受体如趋化因子C-C基序配体2(CCL2)(r = 0.503,P < 0.001)、CXC趋化因子配体12(CXCL12)(r = 0.386,P < 0.001)和CXC趋化因子受体4(CXCR4)(r = 0.492,P < 0.001)以及免疫抑制剂如程序性细胞死亡蛋白1(PDCD1)(r = 0.359,P < 0.001)、细胞毒性T淋巴细胞相关抗原4(CTLA4)(r = 0.375,P < 0.001)和T细胞免疫球蛋白和ITIM结构域(TIGIT)(r = 0.305,P < 0.001)的表达呈正相关。
通过生物信息学分析筛选出肺鳞状细胞癌中的免疫和预后基因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。