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Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy
BACKGROUND: This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. METHOD: RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weight...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454033/ https://www.ncbi.nlm.nih.gov/pubmed/34544443 http://dx.doi.org/10.1186/s12967-021-03078-9 |
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author | Zhou, Yu Wang, Shasha Tao, Yunxia Chen, Haizhu Qin, Yan He, Xiaohui Zhou, Shengyu Liu, Peng Yang, Jianliang Yang, Sheng Gui, Lin Lou, Ning Zhang, Zhishang Yao, Jiarui Han, Xiaohong Shi, Yuankai |
author_facet | Zhou, Yu Wang, Shasha Tao, Yunxia Chen, Haizhu Qin, Yan He, Xiaohui Zhou, Shengyu Liu, Peng Yang, Jianliang Yang, Sheng Gui, Lin Lou, Ning Zhang, Zhishang Yao, Jiarui Han, Xiaohong Shi, Yuankai |
author_sort | Zhou, Yu |
collection | PubMed |
description | BACKGROUND: This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. METHOD: RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. RESULTS: A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. CONCLUSION: CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03078-9. |
format | Online Article Text |
id | pubmed-8454033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-84540332021-09-21 Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy Zhou, Yu Wang, Shasha Tao, Yunxia Chen, Haizhu Qin, Yan He, Xiaohui Zhou, Shengyu Liu, Peng Yang, Jianliang Yang, Sheng Gui, Lin Lou, Ning Zhang, Zhishang Yao, Jiarui Han, Xiaohong Shi, Yuankai J Transl Med Research BACKGROUND: This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. METHOD: RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. RESULTS: A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. CONCLUSION: CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-03078-9. BioMed Central 2021-09-20 /pmc/articles/PMC8454033/ /pubmed/34544443 http://dx.doi.org/10.1186/s12967-021-03078-9 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 Zhou, Yu Wang, Shasha Tao, Yunxia Chen, Haizhu Qin, Yan He, Xiaohui Zhou, Shengyu Liu, Peng Yang, Jianliang Yang, Sheng Gui, Lin Lou, Ning Zhang, Zhishang Yao, Jiarui Han, Xiaohong Shi, Yuankai Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy |
title | Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy |
title_full | Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy |
title_fullStr | Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy |
title_full_unstemmed | Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy |
title_short | Low CCL19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy |
title_sort | low ccl19 expression is associated with adverse clinical outcomes for follicular lymphoma patients treated with chemoimmunotherapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454033/ https://www.ncbi.nlm.nih.gov/pubmed/34544443 http://dx.doi.org/10.1186/s12967-021-03078-9 |
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