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Transcriptomic analysis of tumor tissues and organoids reveals the crucial genes regulating the proliferation of lung adenocarcinoma
BACKGROUND: Accumulative evidence shows that an organoid is a more practical and reliable tool in cancer biology research. This study aimed to identify and validate crucial genes involved in non-small cell lung cancer carcinogenesis and development using the transcriptomic analysis of tumor tissues...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393455/ https://www.ncbi.nlm.nih.gov/pubmed/34446056 http://dx.doi.org/10.1186/s12967-021-03043-6 |
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author | Ma, Xiao Yang, Su Jiang, Hesheng Wang, Yujie Xiang, Zhen |
author_facet | Ma, Xiao Yang, Su Jiang, Hesheng Wang, Yujie Xiang, Zhen |
author_sort | Ma, Xiao |
collection | PubMed |
description | BACKGROUND: Accumulative evidence shows that an organoid is a more practical and reliable tool in cancer biology research. This study aimed to identify and validate crucial genes involved in non-small cell lung cancer carcinogenesis and development using the transcriptomic analysis of tumor tissues and organoids. METHODS: Gene set enrichment analysis (GSEA) of tumor tissues, tumor organoids, and normal tissues was performed to reveal the similar and different mechanisms involved in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) carcinogenesis and progression. Differentially expressed gene analysis, prognostic analysis, and gene co-expression network analysis were further used to identify hub genes involved in LUAD and LUSC carcinogenesis and development. Finally, LUAD cell lines and organoids were used to validate these findings. RESULTS: GSEA analysis was performed to reveal the similar mechanisms involved in LUAD and LUSC carcinogenesis and development, such as P53 signaling pathway, base mismatch repair, DNA replication, cAMP signaling pathway and PPAR pathway. However, comparing with LUSC organoids, LUAD organoids showed downregulation of immune-related pathways, inflammation-related pathways, MAPK signaling pathways, and Rap1 signaling pathways, although these pathways were downregulated in LUAD and LUSC tissues by comparing with normal lung tissues. Further gene co-expression network analysis and prognostic analysis indicated CDK1, CCNB2, and CDC25A as the hub tumor-promoting genes in LUAD but not in LUSC, which were further validated in other datasets. Using LUAD cell lines and organoid models, CDK1 and CCNB2 knockdown were found to suppress LUAD proliferation. However, CDC25A knockdown did not inhibit LUAD cell line proliferation but could effectively suppress LUAD organoid growth, indicating that an organoid could be used as an effective tool to study cancer biology in LUAD. CONCLUSIONS: The results revealed CDK1, CCNB2, and CDC25A as the hub genes involved in LUAD carcinogenesis and development, which could be used as the potential biomarkers and targets for LUAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03043-6. |
format | Online Article Text |
id | pubmed-8393455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83934552021-08-30 Transcriptomic analysis of tumor tissues and organoids reveals the crucial genes regulating the proliferation of lung adenocarcinoma Ma, Xiao Yang, Su Jiang, Hesheng Wang, Yujie Xiang, Zhen J Transl Med Research BACKGROUND: Accumulative evidence shows that an organoid is a more practical and reliable tool in cancer biology research. This study aimed to identify and validate crucial genes involved in non-small cell lung cancer carcinogenesis and development using the transcriptomic analysis of tumor tissues and organoids. METHODS: Gene set enrichment analysis (GSEA) of tumor tissues, tumor organoids, and normal tissues was performed to reveal the similar and different mechanisms involved in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) carcinogenesis and progression. Differentially expressed gene analysis, prognostic analysis, and gene co-expression network analysis were further used to identify hub genes involved in LUAD and LUSC carcinogenesis and development. Finally, LUAD cell lines and organoids were used to validate these findings. RESULTS: GSEA analysis was performed to reveal the similar mechanisms involved in LUAD and LUSC carcinogenesis and development, such as P53 signaling pathway, base mismatch repair, DNA replication, cAMP signaling pathway and PPAR pathway. However, comparing with LUSC organoids, LUAD organoids showed downregulation of immune-related pathways, inflammation-related pathways, MAPK signaling pathways, and Rap1 signaling pathways, although these pathways were downregulated in LUAD and LUSC tissues by comparing with normal lung tissues. Further gene co-expression network analysis and prognostic analysis indicated CDK1, CCNB2, and CDC25A as the hub tumor-promoting genes in LUAD but not in LUSC, which were further validated in other datasets. Using LUAD cell lines and organoid models, CDK1 and CCNB2 knockdown were found to suppress LUAD proliferation. However, CDC25A knockdown did not inhibit LUAD cell line proliferation but could effectively suppress LUAD organoid growth, indicating that an organoid could be used as an effective tool to study cancer biology in LUAD. CONCLUSIONS: The results revealed CDK1, CCNB2, and CDC25A as the hub genes involved in LUAD carcinogenesis and development, which could be used as the potential biomarkers and targets for LUAD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03043-6. BioMed Central 2021-08-26 /pmc/articles/PMC8393455/ /pubmed/34446056 http://dx.doi.org/10.1186/s12967-021-03043-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Ma, Xiao Yang, Su Jiang, Hesheng Wang, Yujie Xiang, Zhen Transcriptomic analysis of tumor tissues and organoids reveals the crucial genes regulating the proliferation of lung adenocarcinoma |
title | Transcriptomic analysis of tumor tissues and organoids reveals the crucial genes regulating the proliferation of lung adenocarcinoma |
title_full | Transcriptomic analysis of tumor tissues and organoids reveals the crucial genes regulating the proliferation of lung adenocarcinoma |
title_fullStr | Transcriptomic analysis of tumor tissues and organoids reveals the crucial genes regulating the proliferation of lung adenocarcinoma |
title_full_unstemmed | Transcriptomic analysis of tumor tissues and organoids reveals the crucial genes regulating the proliferation of lung adenocarcinoma |
title_short | Transcriptomic analysis of tumor tissues and organoids reveals the crucial genes regulating the proliferation of lung adenocarcinoma |
title_sort | transcriptomic analysis of tumor tissues and organoids reveals the crucial genes regulating the proliferation of lung adenocarcinoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393455/ https://www.ncbi.nlm.nih.gov/pubmed/34446056 http://dx.doi.org/10.1186/s12967-021-03043-6 |
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