A Prognostic Nomogram Combining Immune-Related Gene Signature and Clinical Factors Predicts Survival in Patients With Lung Adenocarcinoma

被引:62
|
作者
Song, Congkuan [1 ,2 ,3 ]
Guo, Zixin [1 ,2 ,3 ]
Yu, Donghu [1 ,4 ]
Wang, Yujin [1 ,2 ,3 ]
Wang, Qingwen [1 ,2 ,3 ]
Dong, Zhe [1 ]
Hu, Weidong [1 ,2 ,3 ]
机构
[1] Wuhan Univ, Dept Thorac Surg, Zhongnan Hosp, Wuhan, Peoples R China
[2] Hubei Key Lab Tumor Biol Behav, Wuhan, Hubei, Peoples R China
[3] Hubei Canc Clin Study Ctr, Wuhan, Hubei, Peoples R China
[4] Wuhan Univ, Dept Biol Repositories, Zhongnan Hosp, Wuhan, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2020年 / 10卷
关键词
lung adenocarcinoma; immune related gene; prognosis; signature; nomogram; EPIDIDYMIS PROTEIN 4; TUMOR PURITY; MAL GENE; CANCER; EXPRESSION; HE-4; MICROENVIRONMENT; VALIDATION; NIVOLUMAB; INFILTRATION;
D O I
10.3389/fonc.2020.01300
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The existence of tumor heterogeneity and complex carcinogenic mechanisms in lung adenocarcinoma (LUAD) make the most commonly used TNM staging system unable to well-interpret the prognosis of patients. Using transcriptome profiling and clinical data from The Cancer Genome Atlas (TCGA) database, we constructed an immune signature based on a multivariate Cox analysis (stepwise model). We estimated the half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs in patients according to the pRRophetic algorithm. Gene-set variation analysis (GSVA) was used to reveal pathway enrichment between groups. Moreover, immune microenvironment landscape was described by single-sample gene-set enrichment analysis (ssGSEA) and CIBERSORT and systematically correlated with genomic of these patients. A prognostic nomogram combining the immune signature and TNM stage to predict the prognosis was developed by multivariate Cox regression. The novel signature with four immune-related genes (MAL, MS4A1, OAS1, and WFDC2) had good robustness, which can accurately distinguish between high- and low-risk patients. Compared with low-risk patients, high-risk patients with a worse prognosis (5-year OS: 46.5 vs. 59.4%,p= 0.002) could benefit more from immunotherapy and the application of common chemotherapeutic agents such as cisplatin and paclitaxel (Wilcoxon test, allp< 0.05). There were significant differences in tumor immune microenvironment and metabolic pathways between the two groups. Additionally, the constructed nomogram had reliable predictive performance with the C-index of 0.725 (95% CI = 0.668-0.781) in the development set (n= 500), 0.793 (95% CI = 0.728-0.858) in the internal validation set (n= 250) and 0.679 (95% CI = 0.644-0.714) in the external validation set (n= 442). The corresponding calibration curves also showed good consistency. To sum up, we developed an immune-related gene signature and comprehensively evaluated LUAD immune landscape and metabolic pathways. Effective differentiation of high- and low-risk patients and accurate construction of nomogram would be helpful to the development of individualized treatment strategies.
引用
收藏
页数:16
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