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Differentiated regulation of immune-response related genes between LUAD and LUSC subtypes of lung cancers.

ABSTRACT: Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of lung cancer, with LUSC exhibits faster progression rate than LUAD. To investigate the roles of immune-response related genes (IRGs) in lung cancer progression, we used LUAD and LUSC samples at different cancer progression stages, and identified that the expression profiles of IRGs could serve as a better classification marker for cancerous tissues of both LUAD and LUSC. We found that the expression changes of IRGs were different between LUAD and LUSC. Cell cycle promoting genes, including KIFs and proteasomes, showed faster up-regulation in LUSC, whereas immune response promoting genes, including MHC molecules and chemokines, were more rapidly repressed in LUSC. Comparative pathway analysis revealed that members of the Toll-like receptor and T cell receptor signaling pathways exhibited diverged expression changes between LUAD and LUSC, especially at the early cancer stages. Our results revealed the difference of LUAD and LUSC from the immune response point of view, and provided new clues for the differential treatment of LUAD and LUSC.

SUBMITTER: Chen M

PROVIDER: S-EPMC5352059 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Differentiated regulation of immune-response related genes between LUAD and LUSC subtypes of lung cancers.

Chen Mengzhu M Liu Xiuying X Du Jie J Wang Xiu-Jie XJ Xia Lixin L

Oncotarget 20170101 1

Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two major subtypes of lung cancer, with LUSC exhibits faster progression rate than LUAD. To investigate the roles of immune-response related genes (IRGs) in lung cancer progression, we used LUAD and LUSC samples at different cancer progression stages, and identified that the expression profiles of IRGs could serve as a better classification marker for cancerous tissues of both LUAD and LUSC. We found that the expression c ...[more]

PMID: 27863400

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Project description:BackgroundNon-small cell lung cancer (NSCLC) is a highly heterogeneous malignancy with an extremely high mortality rate. Necroptosis is a programmed cell death mode mediated by three major mediators, RIPK1, RIPK3, and MLKL, and has been shown to play a role in various cancers. To date, the effect of necroptosis on NSCLC remains unclear.MethodsIn The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we downloaded transcriptomes of lung adenocarcinoma (LUAD) patients and their corresponding clinicopathological parameters. We performed multi-omics analysis using consensus clustering based on the expression levels of 40 necroptosis-related genes. We constructed prognostic risk models and used the receiver operating characteristic (ROC) curves, nomograms, and survival analysis to evaluate prognostic models.ResultsWith the use of consensus clustering analysis, two distinct subtypes of necroptosis were identified based on different mRNA expression levels, and cluster B was found to have a better survival advantage. Correlation results showed that necroptosis was significantly linked with clinical features, overall survival (OS) rate, and immune infiltration. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis confirmed that these differential genes were valuable in various cellular and biological functions and were significantly enriched in various pathways such as the P53 signaling pathway and cell cycle. We further identified three genomic subtypes and found that gene cluster B patients had better prognostic value. Multivariate Cox analysis identified the 14 best prognostic genes for constructing prognostic risk models. The high-risk group was found to have a poor prognosis. The construction of nomograms and ROC curves showed stable validity in prognostic prediction. There were also significant differences in tumor immune microenvironment, tumor mutational burden (TMB), and drug sensitivity between the two risk groups. The results demonstrate that the 14 genes constructed in this prognostic risk model were used as tumor prognostic biomarkers to guide immunotherapy and chemotherapy. Finally, we used qRT-PCR to validate the genes involved in the signature.ConclusionThis study promotes our new understanding of necroptosis in the tumor microenvironment of NSCLC, mines prognostic biomarkers, and provides a potential value for guiding immunotherapy and chemotherapy.

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Differentiated regulation of immune-response related genes between LUAD and LUSC subtypes of lung cancers.

Publications

Differentiated regulation of immune-response related genes between LUAD and LUSC subtypes of lung cancers.

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