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pmid:35571020

Apoptosis-Related Signature Predicts Prognosis and Immune Microenvironment Infiltration in Lung Adenocarcinoma.

Xiaoli Zou · Rong He · Zhenzhen Zhang · Yulan Yan

Frontiers in genetics · 2022 doi:10.3389/fgene.2022.818403

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Experiment

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Data

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title
Apoptosis-Related Signature Predicts Prognosis and Immune Microenvironment Infiltration in Lung Adenocarcinoma.
doi
10.3389/fgene.2022.818403
pmid
35571020
authors array · 4 items
[0]
Xiaoli Zou
[1]
Rong He
[2]
Zhenzhen Zhang
[3]
Yulan Yan
journal
Frontiers in genetics
year
2022
abstract
Lung adenocarcinoma (LUAD), a malignancy with high incidence and mortality rates worldwide, contains multiple genomic and epigenomic abnormalities. And the useful tumor markers associated with these abnormalities need further investigation. Whereas apoptosis is a form of programmed cell death, the expression of apoptosis-related genes in LUAD and its relationship with prognosis is unclear. In the present study, we identified 64 differentially expressed apoptosis-related genes (DEARGs) that were differentially expressed between LUAD tissue and normal lung tissue. Based on these DEARGs, all LUAD cases were classified into two subtypes using The Cancer Genome Atlas (TCGA) cohort to assess the prognostic value of apoptosis-related genes for survival. An 11-gene signature was established by applying the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression method to construct a multigene prediction model and classify all LUAD patients in the TCGA cohort into high or low AS-score groups. Patients in the low AS-score group had significantly higher survival and prognosis than those in the high AS-score group. Taking the median risk score of the AS-score, LUAD patients in the GSE68465 cohort were divided into two risk groups, low and high. The overall survival (OS) time was longer in the low AS-score group. Combined with clinical characteristics, the AS-score was an independent predictor of LUAD patients. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analyses showed that the differential genes between the two groups were mainly enriched in cellular immunity. Further analysis revealed higher immune checkpoint protein expression and higher tumor mutational burden (TMB) in the high AS-score group, suggesting better efficacy of immunotherapy in the high AS-score group than the low AS-score group. And the high AS-score group was better in chemotherapy and targeted therapy efficiency. In conclusion, the AS-score constructed based on apoptosis-related genes can predict the prognosis of LUAD patients and provide some guidance for the antitumor treatment of LUAD patients.
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The LASSO-Cox regression model was applied to include 11 of the differential genes with a minimum value of λ(Figures 5B,C).
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sections[15] "Prognostic Gene Modeling in the TCGA Cohort" paragraph 2
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The LASSO-Cox regression model was applied to include 11 of the differential genes with a minimum value of λ(Figures 5B,C).
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The data could be downloaded at (https://portal.gdc.cancer.gov/, https://xenabrowser.net/, and https://www.ncbi.nlm.nih.gov/geo/; GSE68465) and the code used during the current study are available from the corresponding author on reasonable request.
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The data could be downloaded at (https://portal.gdc.cancer.gov/, https://xenabrowser.net/, and https://www.ncbi.nlm.nih.gov/geo/; GSE68465) and the code used during the current study are available from the corresponding author on reasonable request.
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An 11-gene signature was established by applying the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression method to construct a multigene prediction model and classify all LUAD patients in the TCGA cohort into high or low AS-score groups.
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An 11-gene signature was established by applying the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression method to construct a multigene prediction model and classify all LUAD patients in the TCGA cohort into high or low AS-score groups.
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sections[15] "Prognostic Gene Modeling in the TCGA Cohort" paragraph 4
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We found that the area under the ROC curve (AUC) was 0.727 at 1 year, 0.681 at 2 years, and 0.630 at 3 years (Figure 6D).
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An 11-gene signature was established by applying the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression method to construct a multigene prediction model and classify all LUAD patients in the TCGA cohort into high or low AS-score groups.
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caArray_jacob-00182: Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study
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Apoptosis-Related Signature Predicts Prognosis and Imm
[1]
malities need further investigation. Whereas apoptosis is a form of programmed cell death, the expr
[2]
of programmed cell death, the expression of apoptosis-related genes in LUAD and its relationship w
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y, we identified 64 differentially expressed apoptosis-related genes (DEARGs) that were differentia
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ork. Cell Culture The human LUAD cell lines (A549 and PC9) and the normal human lung epithelia
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f Sciences (Shanghai, China). The medium for A549 cells was DMEM medium with 10% fetal bovine
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The LASSO-Cox regression model was applied to include 11 of the differential genes with a minimum value of λ(Figures 5B,C).
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Whereas apoptosis is a form of programmed cell death, the expression of apoptosis-related genes in LUAD and its relationship with prognosis is unclear. In the present study, we identified 64 differentially expressed apoptosis-related genes (DEARGs) that were differentially expressed between LUAD tissue and normal lung tissue. Based on these DEARGs, all LUAD cases were classified into two subtypes using The Cancer Genome Atlas (TCGA) cohort to assess the prognostic value of apoptosis-related genes for survival. An 11-gene signature was established by applying the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression method to construct a multigene prediction model and classify all LUAD patients in the TCGA cohort into high or low AS-score groups. Patients in the low AS-score group had significantly higher survival and prognosis than those in the high AS-score group. Taking the median risk score of the AS-score, LUAD patients in the GSE68465 cohort were divided into two risk groups, low and high. The overall survival (OS) time was longer in the low AS-score group. Combined with clinical characteristics, the AS-score was an independent predictor of LUAD patients. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analyses showed that the differential genes between the two groups were mainly enriched in cellular immunity. Further analysis revealed higher immune checkpoint protein expression and higher tumor mutational burden (TMB) in the high AS-score group, suggesting better efficacy of immunotherapy in the high AS-score group than the low AS-score group. And the high AS-score group was better in chemotherapy and targeted therapy efficiency. 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