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

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 c...

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Published inFrontiers in oncology Vol. 10; p. 1300
Main Authors Song, Congkuan, Guo, Zixin, Yu, Donghu, Wang, Yujin, Wang, Qingwen, Dong, Zhe, Hu, Weidong
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 06.08.2020
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Abstract 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, all p < 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.
AbstractList 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, all p < 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.
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, all p < 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.
Author Yu, Donghu
Guo, Zixin
Dong, Zhe
Hu, Weidong
Song, Congkuan
Wang, Yujin
Wang, Qingwen
AuthorAffiliation 1 Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University , Wuhan , China
2 Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center , Wuhan , China
3 Department of Biological Repositories, Zhongnan Hospital of Wuhan University , Wuhan , China
AuthorAffiliation_xml – name: 2 Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center , Wuhan , China
– name: 3 Department of Biological Repositories, Zhongnan Hospital of Wuhan University , Wuhan , China
– name: 1 Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University , Wuhan , China
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Edited by: Qing Zhou, Guangdong Provincial People's Hospital Lung Cancer Institute, China
Reviewed by: Jai Narendra Patel, Levine Cancer Institute, United States; Juan Hui Wang, Affiliated Cancer Hospital of Zhengzhou University, China
This article was submitted to Thoracic Oncology, a section of the journal Frontiers in Oncology
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Snippet The existence of tumor heterogeneity and complex carcinogenic mechanisms in lung adenocarcinoma (LUAD) make the most commonly used TNM staging system unable to...
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SubjectTerms immune related gene
lung adenocarcinoma
nomogram
Oncology
prognosis
signature
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Title A Prognostic Nomogram Combining Immune-Related Gene Signature and Clinical Factors Predicts Survival in Patients With Lung Adenocarcinoma
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https://pubmed.ncbi.nlm.nih.gov/PMC7424034
https://doaj.org/article/097f6b649c764ec98e6fd4564c265c0f
Volume 10
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