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Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing

BACKGROUND: Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level. METHODS: Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samp...

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Autores principales: Chen, Yingtai, Yin, Jianhua, Zhao, Lulu, Zhou, Guangyu, Dong, Shichen, Zhang, Yueming, Niu, Penghui, Ren, Hu, Zheng, Tianjiao, Yan, Juan, Li, Wenbin, Ma, Peiqin, Zhang, Cuijuan, Wei, Chen, Church, George, Li, Guibo, Zhao, Dongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724296/
https://www.ncbi.nlm.nih.gov/pubmed/36474268
http://dx.doi.org/10.1186/s12967-022-03792-y
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author Chen, Yingtai
Yin, Jianhua
Zhao, Lulu
Zhou, Guangyu
Dong, Shichen
Zhang, Yueming
Niu, Penghui
Ren, Hu
Zheng, Tianjiao
Yan, Juan
Li, Wenbin
Ma, Peiqin
Zhang, Cuijuan
Wei, Chen
Church, George
Li, Guibo
Zhao, Dongbing
author_facet Chen, Yingtai
Yin, Jianhua
Zhao, Lulu
Zhou, Guangyu
Dong, Shichen
Zhang, Yueming
Niu, Penghui
Ren, Hu
Zheng, Tianjiao
Yan, Juan
Li, Wenbin
Ma, Peiqin
Zhang, Cuijuan
Wei, Chen
Church, George
Li, Guibo
Zhao, Dongbing
author_sort Chen, Yingtai
collection PubMed
description BACKGROUND: Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level. METHODS: Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT. RESULTS: Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways were activated in tumor and endothelial cells after treatment, indicating that NACT triggers vascular remodeling by cancer cells together with stromal cells. CONCLUSIONS: In conclusion, our study provided transcriptional profiles of TME between pre-treatment and post-treatment for in-depth understanding on the mechanisms of NACT in gastric cancer and empowering the development of potential optimized therapy procedures and novel drugs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03792-y.
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spelling pubmed-97242962022-12-07 Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing Chen, Yingtai Yin, Jianhua Zhao, Lulu Zhou, Guangyu Dong, Shichen Zhang, Yueming Niu, Penghui Ren, Hu Zheng, Tianjiao Yan, Juan Li, Wenbin Ma, Peiqin Zhang, Cuijuan Wei, Chen Church, George Li, Guibo Zhao, Dongbing J Transl Med Research BACKGROUND: Little is known on the tumor microenvironment (TME) response after neoadjuvant chemotherapy (NACT) in gastric cancer on the molecular level. METHODS: Here, we profiled 33,589 cell transcriptomes in 14 samples from 11 gastric cancer patients (4 pre-treatment samples, 4 post-treatment samples and 3 pre-post pairs) using single-cell RNA sequencing (scRNA-seq) to generate the cell atlas. The ligand-receptor-based intercellular communication networks of the single cells were also characterized before and after NACT. RESULTS: Compered to pre-treatment samples, CD4+ T cells (P = 0.018) and CD8+ T cells (P = 0.010) of post-treatment samples were significantly decreased, while endothelial cells and fibroblasts were increased (P = 0.034 and P = 0.005, respectively). No significant difference observed with respect to CD4+ Tregs cells, cycling T cells, B cells, plasma cells, macrophages, monocytes, dendritic cells, and mast cells (P > 0.05). In the unsupervised nonnegative matrix factorization (NMF) analysis, we revealed that there were three transcriptional programs (NMF1, NMF2 and NMF3) shared among these samples. Compared to pre-treatment samples, signature score of NMF1 was significantly downregulated after treatment (P = 0.009), while the NMF2 signature was significantly upregulated after treatment (P = 0.013). The downregulated NMF1 and upregulated NMF2 signatures were both associated with improved overall survival outcomes based on The Cancer Genome Atlas (TCGA) database. Additionally, proangiogenic pathways were activated in tumor and endothelial cells after treatment, indicating that NACT triggers vascular remodeling by cancer cells together with stromal cells. CONCLUSIONS: In conclusion, our study provided transcriptional profiles of TME between pre-treatment and post-treatment for in-depth understanding on the mechanisms of NACT in gastric cancer and empowering the development of potential optimized therapy procedures and novel drugs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-022-03792-y. BioMed Central 2022-12-06 /pmc/articles/PMC9724296/ /pubmed/36474268 http://dx.doi.org/10.1186/s12967-022-03792-y Text en © The Author(s) 2022 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
Chen, Yingtai
Yin, Jianhua
Zhao, Lulu
Zhou, Guangyu
Dong, Shichen
Zhang, Yueming
Niu, Penghui
Ren, Hu
Zheng, Tianjiao
Yan, Juan
Li, Wenbin
Ma, Peiqin
Zhang, Cuijuan
Wei, Chen
Church, George
Li, Guibo
Zhao, Dongbing
Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing
title Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing
title_full Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing
title_fullStr Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing
title_full_unstemmed Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing
title_short Reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing
title_sort reconstruction of the gastric cancer microenvironment after neoadjuvant chemotherapy by longitudinal single-cell sequencing
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9724296/
https://www.ncbi.nlm.nih.gov/pubmed/36474268
http://dx.doi.org/10.1186/s12967-022-03792-y
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