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pmid:36042374

Identification and validation of a novel prognostic model of inflammation-related gene signature of lung adenocarcinoma.

Dayuan Luo · Wei Feng · Yunqian Ma · Zhibin Jiang

Scientific reports · 2022 doi:10.1038/s41598-022-19105-8

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

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title
Identification and validation of a novel prognostic model of inflammation-related gene signature of lung adenocarcinoma.
doi
10.1038/s41598-022-19105-8
pmid
36042374
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[0]
Dayuan Luo
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Wei Feng
[2]
Yunqian Ma
[3]
Zhibin Jiang
journal
Scientific reports
year
2022
abstract
Previous literatures have suggested the importance of inflammatory response during lung adenocarcinoma (LUAD) development. This study aimed at exploring the inflammation-related genes and developing a prognostic signature for predicting the prognosis of LUAD. Survival‑associated inflammation-related genes were identified by univariate Cox regression analysis in the dataset of The Cancer Genome Atlas (TCGA). The least absolute shrinkage and selection operator (LASSO) penalized Cox regression model was used to derive a risk signature which is significantly negatively correlated with OS and divide samples into high-, medium- and low-risk group. Univariate and multivariate Cox analyses suggested that the level of risk group was an independent prognostic factor of the overall survival (OS). Time-dependent receiver operating characteristic (ROC) curve indicated the AUC of 1-, 3- and 5-years of the risk signature was 0.715, 0.719, 0.699 respectively. A prognostic nomogram was constructed by integrating risk group and clinical features. The independent dataset GSE30219 of Gene Expression Omnibus (GEO) was used for verification. We further explored the differences among risk groups in Gene set enrichment analysis (GSEA), tumor mutation and tumor microenvironment. Furthermore, Single Sample Gene Set Enrichment Analysis (ssGSEA) and the results of Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) suggested the status of immune cell infiltration was highly associated with risk groups. We demonstrated the prediction effect of CTLA-4 and PD-1/PD-L1 inhibitors in the low-risk group was better than that in the high-risk group using two methods of immune score include immunophenoscore from The Cancer Immunome Atlas (TCIA) and TIDE score from Tumor Immune Dysfunction and Exclusion (TIDE). In addition, partial targeted drugs and chemotherapy drugs for lung cancer had higher drug sensitivity in the high-risk group. Our findings provide a foundation for future research targeting inflammation-related genes to predictive prognosis and some reference significance for the selection of immunotherapy and drug regimen for lung adenocarcinoma.
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The least absolute shrinkage and selection operator (LASSO) penalized Cox regression model was used to derive a risk signature which is significantly negatively correlated with OS and divide samples into high-, medium- and low-risk group.
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The least absolute shrinkage and selection operator (LASSO) penalized Cox regression model was used to derive a risk signature which is significantly negatively correlated with OS and divide samples into high-, medium- and low-risk group.
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RNA-seq profiles of LUAD patients were downloaded from the TCGA (https://portal.gdc.cancer.gov/), including fragments per kilobase per million (FPKM). The workflow type is HTSeq-FPKM. R-package “limma” was used to average the repeated data of RNA expression profile. Clinical data of LUAD samples were retrieved and downloaded from TCGA, including gender, age, tumor stage and survival information.
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RNA-seq profiles of LUAD patients were downloaded from the TCGA (https://portal.gdc.cancer.gov/), including fragments per kilobase per million (FPKM). The workflow type is HTSeq-FPKM. R-package “limma” was used to average the repeated data of RNA expression profile. Clinical data of LUAD samples were retrieved and downloaded from TCGA, including gender, age, tumor stage and survival information.
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The LASSO-penalized Cox regression risk signature achieved time-dependent AUC values of 0.715, 0.719, and 0.699 for predicting 1-, 3-, and 5-year overall survival, respectively.
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Time-dependent receiver operating characteristic (ROC) curve indicated the AUC of 1-, 3- and 5-years of the risk signature was 0.715, 0.719, 0.699 respectively.
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RNA-seq profiles of LUAD patients were downloaded from the TCGA (https://portal.gdc.cancer.gov/), including fragments per kilobase per million (FPKM). The workflow type is HTSeq-FPKM. R-package “limma” was used to average the repeated data of RNA expression profile. Clinical data of LUAD samples were retrieved and downloaded from TCGA, including gender, age, tumor stage and survival information.
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Complete file
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This study aimed at exploring the inflammation-related genes and developing a prognostic signature for predicting the prognosis of LUAD. Survival‑associated inflammation-related genes were identified by univariate Cox regression analysis in the dataset of The Cancer Genome Atlas (TCGA). The least absolute shrinkage and selection operator (LASSO) penalized Cox regression model was used to derive a risk signature which is significantly negatively correlated with OS and divide samples into high-, medium- and low-risk group. Univariate and multivariate Cox analyses suggested that the level of risk group was an independent prognostic factor of the overall survival (OS). Time-dependent receiver operating characteristic (ROC) curve indicated the AUC of 1-, 3- and 5-years of the risk signature was 0.715, 0.719, 0.699 respectively. A prognostic nomogram was constructed by integrating risk group and clinical features. The independent dataset GSE30219 of Gene Expression Omnibus (GEO) was used for verification. We further explored the differences among risk groups in Gene set enrichment analysis (GSEA), tumor mutation and tumor microenvironment. Furthermore, Single Sample Gene Set Enrichment Analysis (ssGSEA) and the results of Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) suggested the status of immune cell infiltration was highly associated with risk groups. We demonstrated the prediction effect of CTLA-4 and PD-1/PD-L1 inhibitors in the low-risk group was better than that in the high-risk group using two methods of immune score include immunophenoscore from The Cancer Immunome Atlas (TCIA) and TIDE score from Tumor Immune Dysfunction and Exclusion (TIDE). In addition, partial targeted drugs and chemotherapy drugs for lung cancer had higher drug sensitivity in the high-risk group. 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