A new immune signature for survival prediction and immune checkpoint molecules in non-small cell lung cancer.
A new immune signature for survival prediction and immune checkpoint molecules in non-small cell lung cancer.
复制标题
非小细胞肺癌中的生存预测和免疫检查点分子的新免疫特征。
DOI：
10.3389/fonc.2023.1095313
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发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
免疫检查点阻断（ICB）治疗晚期非小细胞肺癌（NSCLC）带来了显著的临床疗效。然而，预后仍有很大差异。从TCGA数据库、import数据库和IMGT/GENE-DB数据库中提取NSCLC患者免疫相关基因图谱。利用WGCNA构建共表达模块，鉴定出4个共表达模块。鉴定出与肿瘤样本相关性最高的模块枢纽基因。然后进行综合生物信息学分析，揭示参与非小细胞肺癌肿瘤进展和癌症相关免疫学的枢纽基因。采用Cox回归和Lasso回归分析筛选预后特征并建立风险模型。功能分析表明，免疫相关中枢基因参与了免疫细胞的迁移、活化、应答和细胞因子-细胞因子受体相互作用。大多数枢纽基因具有较高的基因扩增频率。MASP1和SEMA5A的突变率最高。M2巨噬细胞与naïve B细胞的比值呈强负相关，CD8 T细胞与活化CD4记忆T细胞的比值呈强正相关。静止肥大细胞预示着更高的总生存率。我们分析了蛋白与蛋白、lncRNA和转录因子之间的相互作用，并通过LASSO回归分析选择了9个基因来构建和验证预后特征。无监督中心基因聚类导致2个不同的NSCLC亚组。2个免疫相关中枢基因亚组的TIDE评分及吉西他滨、顺铂、多西他赛、厄洛替尼、紫杉醇的药物敏感性差异均有统计学意义。这些结果提示，我们的免疫相关基因可以为不同免疫表型的临床诊断和预后提供指导，促进非小细胞肺癌的免疫治疗管理。
Immune checkpoint blockade (ICB) therapy has brought remarkable clinical benefits to patients with advanced non-small cell lung carcinoma (NSCLC). However, the prognosis remains largely variable. The profiles of immune-related genes for patients with NSCLC were extracted from TCGA database, ImmPort dataset, and IMGT/GENE-DB database. Coexpression modules were constructed using WGCNA and 4 modules were identified. The hub genes of the module with the highest correlations with tumor samples were identified. Then integrative bioinformatics analyses were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of NSCLC. Cox regression and Lasso regression analyses were conducted to screen prognostic signature and to develop a risk model. Functional analysis showed that immune-related hub genes were involved in the migration, activation, response, and cytokine-cytokine receptor interaction of immune cells. Most of the hub genes had a high frequency of gene amplifications. MASP1 and SEMA5A presented the highest mutation rate. The ratio of M2 macrophages and naïve B cells revealed a strong negative association while the ratio of CD8 T cells and activated CD4 memory T cells showed a strong positive association. Resting mast cells predicted superior overall survival. Interactions including protein–protein, lncRNA and transcription factor interactions were analyzed and 9 genes were selected by LASSO regression analysis to construct and verify a prognostic signature. Unsupervised hub genes clustering resulted in 2 distinct NSCLC subgroups. The TIDE score and the drug sensitivity of gemcitabine, cisplatin, docetaxel, erlotinib and paclitaxel were significantly different between the 2 immune-related hub gene subgroups. These findings suggested that our immune-related genes can provide clinical guidance for the diagnosis and prognosis of different immunophenotypes and facilitate the management of immunotherapy in NSCLC.
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影响因子：
9.1
作者：
Komi, Daniel Elieh Ali;Redegeld, Frank A.
通讯作者：
Redegeld, Frank A.
影响因子：
45.3
作者：
Kris, Mark G.;Gaspar, Laurie E.;Weyant, Michael
通讯作者：
Weyant, Michael
DOI：
10.1056/nejmoa1714448
发表时间：
2018-02-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Drilon A;Laetsch TW;Kummar S;DuBois SG;Lassen UN;Demetri GD;Nathenson M;Doebele RC;Farago AF;Pappo AS;Turpin B;Dowlati A;Brose MS;Mascarenhas L;Federman N;Berlin J;El-Deiry WS;Baik C;Deeken J;Boni V;Nagasubramanian R;Taylor M;Rudzinski ER;Meric-Bernstam F;Sohal DPS;Ma PC;Raez LE;Hechtman JF;Benayed R;Ladanyi M;Tuch BB;Ebata K;Cruickshank S;Ku NC;Cox MC;Hawkins DS;Hong DS;Hyman DM
通讯作者：
Hyman DM
影响因子：
6.4
作者：
Kanda, Mitsuro;Shimizu, Dai;Kodera, Yasuhiro
通讯作者：
Kodera, Yasuhiro
影响因子：
4.4
作者：
Broderick, L;Yokota, SJ;Bankert, RB
通讯作者：
Bankert, RB