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Identification of a Gene Signature for Renal Cell Carcinoma–Associated Fibroblasts Mediating Cancer Progression and Affecting Prognosis

Background: Cancer-associated fibroblasts (CAFs) are mainly involved in cancer progression and treatment failure. However, the specific signature of CAFs and their related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Here, methods to recognize gene signatures were emp...

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Autores principales: Liu, Bitian, Chen, Xiaonan, Zhan, Yunhong, Wu, Bin, Pan, Shen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901886/
https://www.ncbi.nlm.nih.gov/pubmed/33634098
http://dx.doi.org/10.3389/fcell.2020.604627
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author Liu, Bitian
Chen, Xiaonan
Zhan, Yunhong
Wu, Bin
Pan, Shen
author_facet Liu, Bitian
Chen, Xiaonan
Zhan, Yunhong
Wu, Bin
Pan, Shen
author_sort Liu, Bitian
collection PubMed
description Background: Cancer-associated fibroblasts (CAFs) are mainly involved in cancer progression and treatment failure. However, the specific signature of CAFs and their related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Here, methods to recognize gene signatures were employed to roughly assess the infiltration of CAFs in RCC, based on the data from The Cancer Genome Atlas (TCGA). Weighted Gene Coexpression Network Analysis (WGCNA) was used to cluster transcriptomes and correlate with CAFs to identify the gene signature. Single-cell and cell line sequencing data were used to verify the expression specificity of the gene signature in CAFs. The gene signature was used to evaluate the infiltration of CAFs in each sample, and the clinical significance of each key gene in the gene signature and CAFs was analyzed. We observed that the CAF infiltration was higher in kidney cancer and advanced tumor stage and grade than in normal tissues. The seven key genes of the CAF gene signature identified using WGCNA showed high expression of CAF-related characteristics in the cell clustering landscape and fibroblast cell lines; these genes were found to be associated with extracellular matrix function, collagen synthesis, cell surface interaction, and adhesion. The high CAF infiltration and the key genes were verified from the TCGA and Gene Expression Omnibus data related to the advanced grade, advanced stage, and poor prognosis of RCC. In summary, our findings indicate that the clinically significant gene signature may serve as a potential biomarker of CAFs in RCC, and the infiltration of CAFs is associated with the pathological grade, stage, and prognosis of RCC.
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spelling pubmed-79018862021-02-24 Identification of a Gene Signature for Renal Cell Carcinoma–Associated Fibroblasts Mediating Cancer Progression and Affecting Prognosis Liu, Bitian Chen, Xiaonan Zhan, Yunhong Wu, Bin Pan, Shen Front Cell Dev Biol Cell and Developmental Biology Background: Cancer-associated fibroblasts (CAFs) are mainly involved in cancer progression and treatment failure. However, the specific signature of CAFs and their related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Here, methods to recognize gene signatures were employed to roughly assess the infiltration of CAFs in RCC, based on the data from The Cancer Genome Atlas (TCGA). Weighted Gene Coexpression Network Analysis (WGCNA) was used to cluster transcriptomes and correlate with CAFs to identify the gene signature. Single-cell and cell line sequencing data were used to verify the expression specificity of the gene signature in CAFs. The gene signature was used to evaluate the infiltration of CAFs in each sample, and the clinical significance of each key gene in the gene signature and CAFs was analyzed. We observed that the CAF infiltration was higher in kidney cancer and advanced tumor stage and grade than in normal tissues. The seven key genes of the CAF gene signature identified using WGCNA showed high expression of CAF-related characteristics in the cell clustering landscape and fibroblast cell lines; these genes were found to be associated with extracellular matrix function, collagen synthesis, cell surface interaction, and adhesion. The high CAF infiltration and the key genes were verified from the TCGA and Gene Expression Omnibus data related to the advanced grade, advanced stage, and poor prognosis of RCC. In summary, our findings indicate that the clinically significant gene signature may serve as a potential biomarker of CAFs in RCC, and the infiltration of CAFs is associated with the pathological grade, stage, and prognosis of RCC. Frontiers Media S.A. 2021-02-05 /pmc/articles/PMC7901886/ /pubmed/33634098 http://dx.doi.org/10.3389/fcell.2020.604627 Text en Copyright © 2021 Liu, Chen, Zhan, Wu and Pan. http://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 Cell and Developmental Biology
Liu, Bitian
Chen, Xiaonan
Zhan, Yunhong
Wu, Bin
Pan, Shen
Identification of a Gene Signature for Renal Cell Carcinoma–Associated Fibroblasts Mediating Cancer Progression and Affecting Prognosis
title Identification of a Gene Signature for Renal Cell Carcinoma–Associated Fibroblasts Mediating Cancer Progression and Affecting Prognosis
title_full Identification of a Gene Signature for Renal Cell Carcinoma–Associated Fibroblasts Mediating Cancer Progression and Affecting Prognosis
title_fullStr Identification of a Gene Signature for Renal Cell Carcinoma–Associated Fibroblasts Mediating Cancer Progression and Affecting Prognosis
title_full_unstemmed Identification of a Gene Signature for Renal Cell Carcinoma–Associated Fibroblasts Mediating Cancer Progression and Affecting Prognosis
title_short Identification of a Gene Signature for Renal Cell Carcinoma–Associated Fibroblasts Mediating Cancer Progression and Affecting Prognosis
title_sort identification of a gene signature for renal cell carcinoma–associated fibroblasts mediating cancer progression and affecting prognosis
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901886/
https://www.ncbi.nlm.nih.gov/pubmed/33634098
http://dx.doi.org/10.3389/fcell.2020.604627
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