Development of an Oncogenic Driver Alteration Associated Immune-Related Prognostic Model for Stage I-II Lung Adenocarcinoma
Lung adenocarcinoma (LUAD) needs to be stratified for its heterogeneity. Oncogenic driver alterations such as mutation, translocation, translocation, and mutation predict response to treatment for LUAD. Since oncogenic driver alterations may modulate immune response in tumor microenvironment that ma...
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Published in | Frontiers in oncology Vol. 10; p. 593022 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
28.01.2021
|
Subjects | |
Online Access | Get full text |
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Summary: | Lung adenocarcinoma (LUAD) needs to be stratified for its heterogeneity. Oncogenic driver alterations such as
mutation,
translocation,
translocation, and
mutation predict response to treatment for LUAD. Since oncogenic driver alterations may modulate immune response in tumor microenvironment that may influence prognosis in LUAD, the effects of
,
,
, and
alterations on tumor microenvironment remain unclear. Immune-related prognostic model associated with oncogenic driver alterations is needed. In this study, we performed the Cox-proportional Hazards Analysis based on the L1-penalized (LASSO) Analysis to establish an immune-related prognostic model (IPM) in stage I-II LUAD patients, which was based on 3 immune-related genes (
,
, and
) significantly enriched in patients without
,
,
, and
alterations in The Cancer Genome Atlas (TCGA) database. Then, patients were categorized into high-risk and low-risk groups individually according to the IPM defined risk score. The predicting ability of the IPM was validated in GSE31210 and GSE26939 downloaded from the Gene Expression Omnibus (GEO) database. High-risk was significantly associated with lower overall survival (OS) rates in 3 independent stage I-II LUAD cohorts (all
< 0.05). Moreover, the IPM defined risk independently predicted OS for patients in TCGA stage I-II LUAD cohort (
= 0.011). High-risk group had significantly higher proportions of macrophages M1 and activated mast cells but lower proportions of memory B cells, resting CD4 memory T cells and resting mast cells than low-risk group (all
< 0.05). In addition, the high-risk group had a significantly lower expression of
,
,
, and
than the low-risk group (all
< 0.05). In summary, we established a novel IPM that could provide new biomarkers for risk stratification of stage I-II LUAD patients. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Michael Kiessling, University Hospital Zürich, Switzerland; Sabine Schmid, University Health Network (UHN), Canada These authors have contributed equally to this work and share first authorship This article was submitted to Thoracic Oncology, a section of the journal Frontiers in Oncology Edited by: Sacha I. Rothschild, University of Basel, Switzerland |
ISSN: | 2234-943X 2234-943X |
DOI: | 10.3389/fonc.2020.593022 |