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Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer

Traditionally, cancer-associated fibroblasts (CAFs), an essential component of tumor microenvironment, were exert a crucial part in colon cancer progression. In this study, single-cell RNA-sequencing (scRNA-seq) data from 23 and bulk RNA-seq data from 452 colon cancer patients were extracted from th...

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Autores principales: Zhao, Zhe, Li, Wenqi, Zhu, LiMeng, Xu, Bei, Jiang, Yudong, Ma, Nan, Liu, LiQun, Qiu, Jie, Zhang, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329609/
https://www.ncbi.nlm.nih.gov/pubmed/35910200
http://dx.doi.org/10.3389/fgene.2022.908957
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author Zhao, Zhe
Li, Wenqi
Zhu, LiMeng
Xu, Bei
Jiang, Yudong
Ma, Nan
Liu, LiQun
Qiu, Jie
Zhang, Min
author_facet Zhao, Zhe
Li, Wenqi
Zhu, LiMeng
Xu, Bei
Jiang, Yudong
Ma, Nan
Liu, LiQun
Qiu, Jie
Zhang, Min
author_sort Zhao, Zhe
collection PubMed
description Traditionally, cancer-associated fibroblasts (CAFs), an essential component of tumor microenvironment, were exert a crucial part in colon cancer progression. In this study, single-cell RNA-sequencing (scRNA-seq) data from 23 and bulk RNA-seq data from 452 colon cancer patients were extracted from the GEO database and TCGA-COAD and GEO databases, respectively. From single-cell analysis, 825 differentially expressed genes (DEGs) in CAFs were identified between each pair of six newly defined CAFs, named enCAF, adCAF, vaCAF, meCAF, erCAF, and cyCAF. Cell communication analysis with the iTALK package showed communication relationship between CAFs, including cell autocrine, cytokine, and growth factor subtypes, such as receptor-ligand pairs of TNFSF14-LTBR, IL6-F3, and IL6-IL6ST. Herein, we demonstrated the presence and prognostic value of adCAF and erCAF in colon cancer based on CIBERSORTx, combining single-cell marker genes and transcriptomics data. The prognostic significance of the enCAF and erCAF has been indirectly proved by both the correlation analysis with macrophages and CAFs, and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiment based on 20 paired tumor samples. A prognostic model was constructed with 10 DEGs using the LASSO Cox regression method. The model was validated using two testing datasets, indicate a significant survival accuracy (p < 0.0025). Correlation analyses between clinical information, such as age, gender, tumor stage and tumor features (tumor purity and immune score), and risk scores revealed our CAF-related model’s robustness and excellent performance. Cell infiltration analysis by xCell revealed that the interaction between CAFs and multiple non-specific immune cells such as macrophages and the dendritic cell was a vital factor affecting immune score and prognosis. Finally, we analyzed how common anti-cancer drugs, including camptothecin, docetaxel and bortezomib, and immunotherapy, such as anti-PD-1 treatment, could be different in low-risk and high-risk patients inferred from our CAF-related model. In conclusion, the study utilized refined colon cancer fibroblast subsets and established the prognostic effects from the interaction with nonspecific immune cell.
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spelling pubmed-93296092022-07-29 Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer Zhao, Zhe Li, Wenqi Zhu, LiMeng Xu, Bei Jiang, Yudong Ma, Nan Liu, LiQun Qiu, Jie Zhang, Min Front Genet Genetics Traditionally, cancer-associated fibroblasts (CAFs), an essential component of tumor microenvironment, were exert a crucial part in colon cancer progression. In this study, single-cell RNA-sequencing (scRNA-seq) data from 23 and bulk RNA-seq data from 452 colon cancer patients were extracted from the GEO database and TCGA-COAD and GEO databases, respectively. From single-cell analysis, 825 differentially expressed genes (DEGs) in CAFs were identified between each pair of six newly defined CAFs, named enCAF, adCAF, vaCAF, meCAF, erCAF, and cyCAF. Cell communication analysis with the iTALK package showed communication relationship between CAFs, including cell autocrine, cytokine, and growth factor subtypes, such as receptor-ligand pairs of TNFSF14-LTBR, IL6-F3, and IL6-IL6ST. Herein, we demonstrated the presence and prognostic value of adCAF and erCAF in colon cancer based on CIBERSORTx, combining single-cell marker genes and transcriptomics data. The prognostic significance of the enCAF and erCAF has been indirectly proved by both the correlation analysis with macrophages and CAFs, and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiment based on 20 paired tumor samples. A prognostic model was constructed with 10 DEGs using the LASSO Cox regression method. The model was validated using two testing datasets, indicate a significant survival accuracy (p < 0.0025). Correlation analyses between clinical information, such as age, gender, tumor stage and tumor features (tumor purity and immune score), and risk scores revealed our CAF-related model’s robustness and excellent performance. Cell infiltration analysis by xCell revealed that the interaction between CAFs and multiple non-specific immune cells such as macrophages and the dendritic cell was a vital factor affecting immune score and prognosis. Finally, we analyzed how common anti-cancer drugs, including camptothecin, docetaxel and bortezomib, and immunotherapy, such as anti-PD-1 treatment, could be different in low-risk and high-risk patients inferred from our CAF-related model. In conclusion, the study utilized refined colon cancer fibroblast subsets and established the prognostic effects from the interaction with nonspecific immune cell. Frontiers Media S.A. 2022-07-14 /pmc/articles/PMC9329609/ /pubmed/35910200 http://dx.doi.org/10.3389/fgene.2022.908957 Text en Copyright © 2022 Zhao, Li, Zhu, Xu, Jiang, Ma, Liu, Qiu and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Zhao, Zhe
Li, Wenqi
Zhu, LiMeng
Xu, Bei
Jiang, Yudong
Ma, Nan
Liu, LiQun
Qiu, Jie
Zhang, Min
Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer
title Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer
title_full Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer
title_fullStr Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer
title_full_unstemmed Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer
title_short Construction and Verification of a Fibroblast-Related Prognostic Signature Model for Colon Cancer
title_sort construction and verification of a fibroblast-related prognostic signature model for colon cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329609/
https://www.ncbi.nlm.nih.gov/pubmed/35910200
http://dx.doi.org/10.3389/fgene.2022.908957
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