Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses

BackgroundImmunotherapy has gradually become an important therapy option for lung cancer patients.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were responsible for all the public data.ResultsIn our study, we firstly identified 22 characteristic genes of NSCLC imm...

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Main Authors: Xunlang Zhang, Xinhui Wu, Huang Huang, Kangming Du, Yingying Nie, Peiyuan Su, Yuefei Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.1014333/full
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author Xunlang Zhang
Xinhui Wu
Huang Huang
Kangming Du
Yingying Nie
Peiyuan Su
Yuefei Li
author_facet Xunlang Zhang
Xinhui Wu
Huang Huang
Kangming Du
Yingying Nie
Peiyuan Su
Yuefei Li
author_sort Xunlang Zhang
collection DOAJ
description BackgroundImmunotherapy has gradually become an important therapy option for lung cancer patients.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were responsible for all the public data.ResultsIn our study, we firstly identified 22 characteristic genes of NSCLC immunotherapy response using the machine learning algorithm. Molecule subtyping was then conducted and two patient subtypes were identified Cluster1 and Cluster2. Results showed that Cluster1 patients had a lower TIDE score and were more sensitive to immunotherapy in both TCGA and combined GEO cohorts. Biological enrichment analysis showed that pathways of epithelial-mesenchymal transition (EMT), apical junction, KRAS signaling, myogenesis, G2M checkpoint, E2F targets, WNT/β-catenin signaling, hedgehog signaling, hypoxia were activated in Cluster2 patients. Genomic instability between Cluster1 and Cluster2 patients was not significantly different. Interestingly, we found that female patients were more adaptable to immunotherapy. Biological enrichment revealed that compared with female patients, pathways of MYC target, G2M checkpoints, mTORC1 signaling, MYC target, E2F target, KRAS signaling, oxidative phosphorylation, mitotic spindle and P53 pathway were activated. Meanwhile, monocytes might have a potential role in affecting NSCLC immunotherapy and underlying mechanism has been explored. Finally, we found that SEC14L3 and APCDD1L were the underlying targets affecting immunotherapy, as well as patients survival.ConclusionsThese results can provide direction and guidance for future research focused on NSCLC immunotherapy.
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spelling doaj.art-684574bd02874460a8c74186605499492022-12-22T02:03:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.10143331014333Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responsesXunlang Zhang0Xinhui Wu1Huang Huang2Kangming Du3Yingying Nie4Peiyuan Su5Yuefei Li6Department of Geriatric, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Geriatric, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Cardiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Vascular Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Ophthalmology, Ineye Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Cardiothoracic Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Anesthesiology Operating Room, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaBackgroundImmunotherapy has gradually become an important therapy option for lung cancer patients.MethodsThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were responsible for all the public data.ResultsIn our study, we firstly identified 22 characteristic genes of NSCLC immunotherapy response using the machine learning algorithm. Molecule subtyping was then conducted and two patient subtypes were identified Cluster1 and Cluster2. Results showed that Cluster1 patients had a lower TIDE score and were more sensitive to immunotherapy in both TCGA and combined GEO cohorts. Biological enrichment analysis showed that pathways of epithelial-mesenchymal transition (EMT), apical junction, KRAS signaling, myogenesis, G2M checkpoint, E2F targets, WNT/β-catenin signaling, hedgehog signaling, hypoxia were activated in Cluster2 patients. Genomic instability between Cluster1 and Cluster2 patients was not significantly different. Interestingly, we found that female patients were more adaptable to immunotherapy. Biological enrichment revealed that compared with female patients, pathways of MYC target, G2M checkpoints, mTORC1 signaling, MYC target, E2F target, KRAS signaling, oxidative phosphorylation, mitotic spindle and P53 pathway were activated. Meanwhile, monocytes might have a potential role in affecting NSCLC immunotherapy and underlying mechanism has been explored. Finally, we found that SEC14L3 and APCDD1L were the underlying targets affecting immunotherapy, as well as patients survival.ConclusionsThese results can provide direction and guidance for future research focused on NSCLC immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1014333/fulllung cancerimmunotherapygendermonocytesmolecules
spellingShingle Xunlang Zhang
Xinhui Wu
Huang Huang
Kangming Du
Yingying Nie
Peiyuan Su
Yuefei Li
Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses
Frontiers in Immunology
lung cancer
immunotherapy
gender
monocytes
molecules
title Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses
title_full Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses
title_fullStr Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses
title_full_unstemmed Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses
title_short Research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses
title_sort research into the biological differences and targets in lung cancer patients with diverse immunotherapy responses
topic lung cancer
immunotherapy
gender
monocytes
molecules
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.1014333/full
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