Cargando…

Integrated Multiomics Analyses Revealing Different Molecular Profiles Between Early- and Late-Stage Lung Adenocarcinoma

The molecular differences in genetic and epigenetic profiling between early-stage (ES) and late-stage (LS) lung adenocarcinoma (LUAD), which might help to understand cancer progression and biomarker guided precision treatment, need further be investigated. In this study, we performed comprehensive a...

Descripción completa

Detalles Bibliográficos
Autores principales: Yue, Dongsheng, Liu, Weiran, Gao, Liuwei, Zhang, Lianmin, Wang, Tao, Xiao, Shanshan, Fu, Yingxue, Li, Nan, Lin, Rui, Hu, Yao, Ding, Lieming, Zhang, Zhenfa, Zhang, Bin, Wang, Changli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567144/
https://www.ncbi.nlm.nih.gov/pubmed/34745971
http://dx.doi.org/10.3389/fonc.2021.746943
_version_ 1784594172900016128
author Yue, Dongsheng
Liu, Weiran
Gao, Liuwei
Zhang, Lianmin
Wang, Tao
Xiao, Shanshan
Fu, Yingxue
Li, Nan
Lin, Rui
Hu, Yao
Ding, Lieming
Zhang, Zhenfa
Zhang, Bin
Wang, Changli
author_facet Yue, Dongsheng
Liu, Weiran
Gao, Liuwei
Zhang, Lianmin
Wang, Tao
Xiao, Shanshan
Fu, Yingxue
Li, Nan
Lin, Rui
Hu, Yao
Ding, Lieming
Zhang, Zhenfa
Zhang, Bin
Wang, Changli
author_sort Yue, Dongsheng
collection PubMed
description The molecular differences in genetic and epigenetic profiling between early-stage (ES) and late-stage (LS) lung adenocarcinoma (LUAD), which might help to understand cancer progression and biomarker guided precision treatment, need further be investigated. In this study, we performed comprehensive analysis using multi-omics next-generation sequencing (NGS) on tissue samples from 7 ES (stage I) and 10 LS (stage III/IV) LUAD patients to study molecular characteristics between the two groups. Characterization of the genomic and transcriptomic profiles showed stage-specific somatic mutations, copy number variations (CNVs) and differentially expressed genes (DEGs). LS samples tend to have more TP53, ERBB2 and CHD4 mutations. Gene copy number loss occurs in immune-related gene pathways in the late stage of LUAD. ATAC-seq analysis showed that LS samples harbored more open chromatin peaks around promoter regions and transcription start sites (TSS) than ES samples. We then identified the known transcription factor (TF) binding motifs for the differentially abundant ATAC-seq peaks between the ES and LS samples and found distinct regulatory mechanisms related to each stage. Furthermore, integrative analysis of ATAC-seq with WGS and RNA-seq data showed that the degree of chromatin accessibility is related to copy number changes, and the open chromatin regions could directly regulate the expression of some DEGs. In conclusion, we performed a comprehensive multi-omics analysis of the early and late stages of LUAD and highlighted some important molecular differences in regulatory mechanisms during cancer progression. Those findings help to further understand mechanism and biomarker related targeted therapy.
format Online
Article
Text
id pubmed-8567144
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85671442021-11-05 Integrated Multiomics Analyses Revealing Different Molecular Profiles Between Early- and Late-Stage Lung Adenocarcinoma Yue, Dongsheng Liu, Weiran Gao, Liuwei Zhang, Lianmin Wang, Tao Xiao, Shanshan Fu, Yingxue Li, Nan Lin, Rui Hu, Yao Ding, Lieming Zhang, Zhenfa Zhang, Bin Wang, Changli Front Oncol Oncology The molecular differences in genetic and epigenetic profiling between early-stage (ES) and late-stage (LS) lung adenocarcinoma (LUAD), which might help to understand cancer progression and biomarker guided precision treatment, need further be investigated. In this study, we performed comprehensive analysis using multi-omics next-generation sequencing (NGS) on tissue samples from 7 ES (stage I) and 10 LS (stage III/IV) LUAD patients to study molecular characteristics between the two groups. Characterization of the genomic and transcriptomic profiles showed stage-specific somatic mutations, copy number variations (CNVs) and differentially expressed genes (DEGs). LS samples tend to have more TP53, ERBB2 and CHD4 mutations. Gene copy number loss occurs in immune-related gene pathways in the late stage of LUAD. ATAC-seq analysis showed that LS samples harbored more open chromatin peaks around promoter regions and transcription start sites (TSS) than ES samples. We then identified the known transcription factor (TF) binding motifs for the differentially abundant ATAC-seq peaks between the ES and LS samples and found distinct regulatory mechanisms related to each stage. Furthermore, integrative analysis of ATAC-seq with WGS and RNA-seq data showed that the degree of chromatin accessibility is related to copy number changes, and the open chromatin regions could directly regulate the expression of some DEGs. In conclusion, we performed a comprehensive multi-omics analysis of the early and late stages of LUAD and highlighted some important molecular differences in regulatory mechanisms during cancer progression. Those findings help to further understand mechanism and biomarker related targeted therapy. Frontiers Media S.A. 2021-10-21 /pmc/articles/PMC8567144/ /pubmed/34745971 http://dx.doi.org/10.3389/fonc.2021.746943 Text en Copyright © 2021 Yue, Liu, Gao, Zhang, Wang, Xiao, Fu, Li, Lin, Hu, Ding, Zhang, Zhang and Wang 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 Oncology
Yue, Dongsheng
Liu, Weiran
Gao, Liuwei
Zhang, Lianmin
Wang, Tao
Xiao, Shanshan
Fu, Yingxue
Li, Nan
Lin, Rui
Hu, Yao
Ding, Lieming
Zhang, Zhenfa
Zhang, Bin
Wang, Changli
Integrated Multiomics Analyses Revealing Different Molecular Profiles Between Early- and Late-Stage Lung Adenocarcinoma
title Integrated Multiomics Analyses Revealing Different Molecular Profiles Between Early- and Late-Stage Lung Adenocarcinoma
title_full Integrated Multiomics Analyses Revealing Different Molecular Profiles Between Early- and Late-Stage Lung Adenocarcinoma
title_fullStr Integrated Multiomics Analyses Revealing Different Molecular Profiles Between Early- and Late-Stage Lung Adenocarcinoma
title_full_unstemmed Integrated Multiomics Analyses Revealing Different Molecular Profiles Between Early- and Late-Stage Lung Adenocarcinoma
title_short Integrated Multiomics Analyses Revealing Different Molecular Profiles Between Early- and Late-Stage Lung Adenocarcinoma
title_sort integrated multiomics analyses revealing different molecular profiles between early- and late-stage lung adenocarcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567144/
https://www.ncbi.nlm.nih.gov/pubmed/34745971
http://dx.doi.org/10.3389/fonc.2021.746943
work_keys_str_mv AT yuedongsheng integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT liuweiran integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT gaoliuwei integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT zhanglianmin integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT wangtao integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT xiaoshanshan integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT fuyingxue integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT linan integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT linrui integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT huyao integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT dinglieming integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT zhangzhenfa integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT zhangbin integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma
AT wangchangli integratedmultiomicsanalysesrevealingdifferentmolecularprofilesbetweenearlyandlatestagelungadenocarcinoma