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Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma

ADME genes are a set of genes which are involved in drug absorption, distribution, metabolism, and excretion (ADME). However, prognostic value and function of ADME genes in head and neck squamous cell carcinoma (HNSCC) remain largely unclear. In this study, we established an ADME-related prognostic...

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Autores principales: Tang, Xinran, Li, Rui, Wu, Dehua, Wang, Yikai, Zhao, Fang, Lv, Ruxue, Wen, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304892/
https://www.ncbi.nlm.nih.gov/pubmed/35874705
http://dx.doi.org/10.3389/fimmu.2022.905635
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author Tang, Xinran
Li, Rui
Wu, Dehua
Wang, Yikai
Zhao, Fang
Lv, Ruxue
Wen, Xin
author_facet Tang, Xinran
Li, Rui
Wu, Dehua
Wang, Yikai
Zhao, Fang
Lv, Ruxue
Wen, Xin
author_sort Tang, Xinran
collection PubMed
description ADME genes are a set of genes which are involved in drug absorption, distribution, metabolism, and excretion (ADME). However, prognostic value and function of ADME genes in head and neck squamous cell carcinoma (HNSCC) remain largely unclear. In this study, we established an ADME-related prognostic model through the least absolute shrinkage and selection operator (LASSO) analysis in the Cancer Genome Atla (TCGA) training cohort and its robustness was validated by TCGA internal validation cohort and a Gene Expression Omnibus (GEO) external cohort. The 14-gene signature stratified patients into high- or low-risk groups. Patients with high-risk scores exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than those with low-risk scores. Receiver operating characteristic (ROC) curve analysis was used to confirm the signature’s predictive efficacy for OS and DFS. Furthermore, gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses showed that immune-related functions and pathways were enriched, such as lymphocyte activation, leukocyte cell-cell adhesion and T-helper cell differentiation. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and other analyses revealed that immune cell (especially B cell and T cell) infiltration levels were significantly higher in the low-risk group. Moreover, patients with low-risk scores were significantly associated with immunotherapy and chemotherapy treatment benefit. In conclusion, we constructed a novel ADME-related prognostic and therapeutic biomarker associated with immune cell infiltration of HNSCC patients.
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spelling pubmed-93048922022-07-23 Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma Tang, Xinran Li, Rui Wu, Dehua Wang, Yikai Zhao, Fang Lv, Ruxue Wen, Xin Front Immunol Immunology ADME genes are a set of genes which are involved in drug absorption, distribution, metabolism, and excretion (ADME). However, prognostic value and function of ADME genes in head and neck squamous cell carcinoma (HNSCC) remain largely unclear. In this study, we established an ADME-related prognostic model through the least absolute shrinkage and selection operator (LASSO) analysis in the Cancer Genome Atla (TCGA) training cohort and its robustness was validated by TCGA internal validation cohort and a Gene Expression Omnibus (GEO) external cohort. The 14-gene signature stratified patients into high- or low-risk groups. Patients with high-risk scores exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than those with low-risk scores. Receiver operating characteristic (ROC) curve analysis was used to confirm the signature’s predictive efficacy for OS and DFS. Furthermore, gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses showed that immune-related functions and pathways were enriched, such as lymphocyte activation, leukocyte cell-cell adhesion and T-helper cell differentiation. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and other analyses revealed that immune cell (especially B cell and T cell) infiltration levels were significantly higher in the low-risk group. Moreover, patients with low-risk scores were significantly associated with immunotherapy and chemotherapy treatment benefit. In conclusion, we constructed a novel ADME-related prognostic and therapeutic biomarker associated with immune cell infiltration of HNSCC patients. Frontiers Media S.A. 2022-07-08 /pmc/articles/PMC9304892/ /pubmed/35874705 http://dx.doi.org/10.3389/fimmu.2022.905635 Text en Copyright © 2022 Tang, Li, Wu, Wang, Zhao, Lv and Wen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Tang, Xinran
Li, Rui
Wu, Dehua
Wang, Yikai
Zhao, Fang
Lv, Ruxue
Wen, Xin
Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma
title Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma
title_full Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma
title_fullStr Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma
title_full_unstemmed Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma
title_short Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma
title_sort development and validation of an adme-related gene signature for survival, treatment outcome and immune cell infiltration in head and neck squamous cell carcinoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304892/
https://www.ncbi.nlm.nih.gov/pubmed/35874705
http://dx.doi.org/10.3389/fimmu.2022.905635
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