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An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes
The effects of methylation/autophagy-related genes (MARGs) and immune infiltration in the tumor microenvironment on the prognosis of laryngeal cancer were comprehensively explored in this study. Survival analysis screened out 126 MARGs and 10 immune cells potentially associated with the prognosis of...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176413/ https://www.ncbi.nlm.nih.gov/pubmed/34093817 http://dx.doi.org/10.7150/jca.58076 |
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author | Kang, Xueran Chen, Yisheng Yi, Bin Yan, Xiaojun Jiang, Chenyan Chen, Bin Lu, Lixing Sun, Yuxing Shi, Runjie |
author_facet | Kang, Xueran Chen, Yisheng Yi, Bin Yan, Xiaojun Jiang, Chenyan Chen, Bin Lu, Lixing Sun, Yuxing Shi, Runjie |
author_sort | Kang, Xueran |
collection | PubMed |
description | The effects of methylation/autophagy-related genes (MARGs) and immune infiltration in the tumor microenvironment on the prognosis of laryngeal cancer were comprehensively explored in this study. Survival analysis screened out 126 MARGs and 10 immune cells potentially associated with the prognosis of laryngeal carcinoma. Cox and lasso regression analyses were then used to select 8 MARGs (CAPN10, DAPK2, MBTPS2, ST13, CFLAR, FADD, PEX14 and TSC2) and 2 immune cells (Eosinophil and Mast cell) to obtain the prognostic risk scoring system (pRS). The pRS was used to establish a risk prediction model for the prognosis of laryngeal cancer. The predictive ability of the prediction model was evaluated by GEO datasets and our clinical samples. Further analysis revealed that pRS is highly associated with single nucleotide polymorphism (SNP), copy number variation (CNV), immune checkpoint blockade (ICB) therapy and tumor microenvironment. Moreover, the screened pRS-related ceRNA network and circ_0002951/miR-548k/HAS2 pathway provide potential therapeutic targets and biomarkers of laryngocarcinoma. Based on the clustering results of pRS-related genes, single cells were then genotyped and revealed by integrated scRNA-seq in laryngeal cancer samples. Fibroblasts were found enriched in high risk cell clusters at the scRNA-seq level. Fibroblast-related ligand-receptor interactions were then exposed and a neural network-based deep learning model based on these pRS-related hub gene signatures was also established with a high accuracy in cell type prediction. In conclusion, the combination of single-cell and transcriptome laryngeal carcinoma landscape analyses can investigate the link between the tumor microenvironmental and prognostic characteristics. |
format | Online Article Text |
id | pubmed-8176413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-81764132021-06-04 An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes Kang, Xueran Chen, Yisheng Yi, Bin Yan, Xiaojun Jiang, Chenyan Chen, Bin Lu, Lixing Sun, Yuxing Shi, Runjie J Cancer Research Paper The effects of methylation/autophagy-related genes (MARGs) and immune infiltration in the tumor microenvironment on the prognosis of laryngeal cancer were comprehensively explored in this study. Survival analysis screened out 126 MARGs and 10 immune cells potentially associated with the prognosis of laryngeal carcinoma. Cox and lasso regression analyses were then used to select 8 MARGs (CAPN10, DAPK2, MBTPS2, ST13, CFLAR, FADD, PEX14 and TSC2) and 2 immune cells (Eosinophil and Mast cell) to obtain the prognostic risk scoring system (pRS). The pRS was used to establish a risk prediction model for the prognosis of laryngeal cancer. The predictive ability of the prediction model was evaluated by GEO datasets and our clinical samples. Further analysis revealed that pRS is highly associated with single nucleotide polymorphism (SNP), copy number variation (CNV), immune checkpoint blockade (ICB) therapy and tumor microenvironment. Moreover, the screened pRS-related ceRNA network and circ_0002951/miR-548k/HAS2 pathway provide potential therapeutic targets and biomarkers of laryngocarcinoma. Based on the clustering results of pRS-related genes, single cells were then genotyped and revealed by integrated scRNA-seq in laryngeal cancer samples. Fibroblasts were found enriched in high risk cell clusters at the scRNA-seq level. Fibroblast-related ligand-receptor interactions were then exposed and a neural network-based deep learning model based on these pRS-related hub gene signatures was also established with a high accuracy in cell type prediction. In conclusion, the combination of single-cell and transcriptome laryngeal carcinoma landscape analyses can investigate the link between the tumor microenvironmental and prognostic characteristics. Ivyspring International Publisher 2021-05-13 /pmc/articles/PMC8176413/ /pubmed/34093817 http://dx.doi.org/10.7150/jca.58076 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Kang, Xueran Chen, Yisheng Yi, Bin Yan, Xiaojun Jiang, Chenyan Chen, Bin Lu, Lixing Sun, Yuxing Shi, Runjie An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes |
title | An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes |
title_full | An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes |
title_fullStr | An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes |
title_full_unstemmed | An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes |
title_short | An integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes |
title_sort | integrative microenvironment approach for laryngeal carcinoma: the role of immune/methylation/autophagy signatures on disease clinical prognosis and single-cell genotypes |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176413/ https://www.ncbi.nlm.nih.gov/pubmed/34093817 http://dx.doi.org/10.7150/jca.58076 |
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