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Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma

BACKGROUND: Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily unexplored in lung adenocarcinoma (LUAD)....

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Autores principales: Ge, Xiaoyong, Liu, Zaoqu, Weng, Siyuan, Xu, Hui, Zhang, Yuyuan, Liu, Long, Dang, Qin, Guo, Chunguang, Beatson, Richard, Deng, Jinhai, Han, Xinwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271977/
https://www.ncbi.nlm.nih.gov/pubmed/35832634
http://dx.doi.org/10.1016/j.csbj.2022.06.064
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author Ge, Xiaoyong
Liu, Zaoqu
Weng, Siyuan
Xu, Hui
Zhang, Yuyuan
Liu, Long
Dang, Qin
Guo, Chunguang
Beatson, Richard
Deng, Jinhai
Han, Xinwei
author_facet Ge, Xiaoyong
Liu, Zaoqu
Weng, Siyuan
Xu, Hui
Zhang, Yuyuan
Liu, Long
Dang, Qin
Guo, Chunguang
Beatson, Richard
Deng, Jinhai
Han, Xinwei
author_sort Ge, Xiaoyong
collection PubMed
description BACKGROUND: Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily unexplored in lung adenocarcinoma (LUAD). METHODS: A total of 2065 samples were recruited from eight independent cohorts. Pharmacogenomics data were generated from the profiling of relative inhibition simultaneously in mixtures (PRISM) and the genomics of drug sensitivity in cancer (GDSC) databases. Multiple bioinformatics approaches were performed to identify pharmacogenomics-based subtypes and find subtype-specific properties. RESULTS: Three reproducible molecular subtypes were found, which were independent prognostic factors and highly associated with stage, survival status, and accepted molecular subtypes. Pharmacogenomics-based subtypes had distinct molecular characteristics: S-Ⅰ was inflammatory, proliferative, and immune-evasion; S-Ⅱ was proliferative and genetics-driven; S-III was metabolic and methylation-driven. Finally, our study provided subtype-guided personalized treatment strategies: Immune checkpoint blockers (ICBs), doxorubicin, tipifarnib, AZ628, and AZD6244 were for S-Ⅰ; Cisplatin, camptothecin, roscovitine, and A.443654 were for S-Ⅱ; Docetaxel, paclitaxel, vinorelbine, and BIBW2992 were for S-III. CONCLUSION: We provided a novel molecular classification strategy and revealed three pharmacogenomics-based subtypes for LUAD patients, which uncovered potential subtype-related and patient-specific therapeutic strategies.
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spelling pubmed-92719772022-07-12 Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma Ge, Xiaoyong Liu, Zaoqu Weng, Siyuan Xu, Hui Zhang, Yuyuan Liu, Long Dang, Qin Guo, Chunguang Beatson, Richard Deng, Jinhai Han, Xinwei Comput Struct Biotechnol J Research Article BACKGROUND: Pharmacogenomics is crucial for individualized drug therapy and plays an increasingly vital role in precision medicine decision-making. However, pharmacogenomics-based molecular subtypes and their potential clinical significance remain primarily unexplored in lung adenocarcinoma (LUAD). METHODS: A total of 2065 samples were recruited from eight independent cohorts. Pharmacogenomics data were generated from the profiling of relative inhibition simultaneously in mixtures (PRISM) and the genomics of drug sensitivity in cancer (GDSC) databases. Multiple bioinformatics approaches were performed to identify pharmacogenomics-based subtypes and find subtype-specific properties. RESULTS: Three reproducible molecular subtypes were found, which were independent prognostic factors and highly associated with stage, survival status, and accepted molecular subtypes. Pharmacogenomics-based subtypes had distinct molecular characteristics: S-Ⅰ was inflammatory, proliferative, and immune-evasion; S-Ⅱ was proliferative and genetics-driven; S-III was metabolic and methylation-driven. Finally, our study provided subtype-guided personalized treatment strategies: Immune checkpoint blockers (ICBs), doxorubicin, tipifarnib, AZ628, and AZD6244 were for S-Ⅰ; Cisplatin, camptothecin, roscovitine, and A.443654 were for S-Ⅱ; Docetaxel, paclitaxel, vinorelbine, and BIBW2992 were for S-III. CONCLUSION: We provided a novel molecular classification strategy and revealed three pharmacogenomics-based subtypes for LUAD patients, which uncovered potential subtype-related and patient-specific therapeutic strategies. Research Network of Computational and Structural Biotechnology 2022-07-02 /pmc/articles/PMC9271977/ /pubmed/35832634 http://dx.doi.org/10.1016/j.csbj.2022.06.064 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Ge, Xiaoyong
Liu, Zaoqu
Weng, Siyuan
Xu, Hui
Zhang, Yuyuan
Liu, Long
Dang, Qin
Guo, Chunguang
Beatson, Richard
Deng, Jinhai
Han, Xinwei
Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma
title Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma
title_full Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma
title_fullStr Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma
title_full_unstemmed Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma
title_short Integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma
title_sort integrative pharmacogenomics revealed three subtypes with different immune landscapes and specific therapeutic responses in lung adenocarcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271977/
https://www.ncbi.nlm.nih.gov/pubmed/35832634
http://dx.doi.org/10.1016/j.csbj.2022.06.064
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