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Coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma
In recent years, personalized cancer immunotherapy, especially stratification-driven precision treatments have gained significant traction. However, due to the heterogeneity in clinical cohorts, the uncombined analysis of stratification/therapeutics may lead to confusion in determining ideal therape...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485744/ https://www.ncbi.nlm.nih.gov/pubmed/32855362 http://dx.doi.org/10.18632/aging.103775 |
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author | Hu, Weilei Wang, Guosheng Chen, Yundi Yarmus, Lonny B. Liu, Biao Wan, Yuan |
author_facet | Hu, Weilei Wang, Guosheng Chen, Yundi Yarmus, Lonny B. Liu, Biao Wan, Yuan |
author_sort | Hu, Weilei |
collection | PubMed |
description | In recent years, personalized cancer immunotherapy, especially stratification-driven precision treatments have gained significant traction. However, due to the heterogeneity in clinical cohorts, the uncombined analysis of stratification/therapeutics may lead to confusion in determining ideal therapeutic options. We report that the coupled immune stratification and drug repurposing could facilitate identification of therapeutic candidates in patients with lung adenocarcinoma (LUAD). First, we categorized the patients into four groups based on immune gene profiling, associated with distinct molecular characteristics and clinical outcomes. Then, the weighted gene co-expression network analysis (WGCNA) algorithm was used to identify co-expression modules of each groups. We focused on C3 group which is characterized by low immune infiltration (cold tumor) and wild-type EGFR, posing a significant challenge for treatment of LUAD. Five drug candidates against the C3 status were identified which have potential dual functions to correct aberrant immune microenvironment and also halt tumorigenesis. Furthermore, their steady binding affinity against the targets was verified through molecular docking analysis. In sum, our findings suggest that such coupled analysis could be a promising methodology for identification and exploration of therapeutic candidates in the practice of personalized immunotherapy. |
format | Online Article Text |
id | pubmed-7485744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-74857442020-09-14 Coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma Hu, Weilei Wang, Guosheng Chen, Yundi Yarmus, Lonny B. Liu, Biao Wan, Yuan Aging (Albany NY) Research Paper In recent years, personalized cancer immunotherapy, especially stratification-driven precision treatments have gained significant traction. However, due to the heterogeneity in clinical cohorts, the uncombined analysis of stratification/therapeutics may lead to confusion in determining ideal therapeutic options. We report that the coupled immune stratification and drug repurposing could facilitate identification of therapeutic candidates in patients with lung adenocarcinoma (LUAD). First, we categorized the patients into four groups based on immune gene profiling, associated with distinct molecular characteristics and clinical outcomes. Then, the weighted gene co-expression network analysis (WGCNA) algorithm was used to identify co-expression modules of each groups. We focused on C3 group which is characterized by low immune infiltration (cold tumor) and wild-type EGFR, posing a significant challenge for treatment of LUAD. Five drug candidates against the C3 status were identified which have potential dual functions to correct aberrant immune microenvironment and also halt tumorigenesis. Furthermore, their steady binding affinity against the targets was verified through molecular docking analysis. In sum, our findings suggest that such coupled analysis could be a promising methodology for identification and exploration of therapeutic candidates in the practice of personalized immunotherapy. Impact Journals 2020-08-27 /pmc/articles/PMC7485744/ /pubmed/32855362 http://dx.doi.org/10.18632/aging.103775 Text en Copyright © 2020 Hu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Hu, Weilei Wang, Guosheng Chen, Yundi Yarmus, Lonny B. Liu, Biao Wan, Yuan Coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma |
title | Coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma |
title_full | Coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma |
title_fullStr | Coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma |
title_full_unstemmed | Coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma |
title_short | Coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma |
title_sort | coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485744/ https://www.ncbi.nlm.nih.gov/pubmed/32855362 http://dx.doi.org/10.18632/aging.103775 |
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