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TGF-β Pathways Stratify Colorectal Cancer into Two Subtypes with Distinct Cartilage Oligomeric Matrix Protein (COMP) Expression-Related Characteristics
Background: Colorectal cancers (CRCs) continue to be the leading cause of cancer-related deaths worldwide. The exact landscape of the molecular features of TGF-β pathway-inducing CRCs remains uncharacterized. Methods: Unsupervised hierarchical clustering was performed to stratify samples into two cl...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775768/ https://www.ncbi.nlm.nih.gov/pubmed/36551305 http://dx.doi.org/10.3390/biom12121877 |
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author | Ding, Jia-Tong Zhou, Hao-Nan Huang, Ying-Feng Peng, Jie Huang, Hao-Yu Yi, Hao Zong, Zhen Ning, Zhi-Kun |
author_facet | Ding, Jia-Tong Zhou, Hao-Nan Huang, Ying-Feng Peng, Jie Huang, Hao-Yu Yi, Hao Zong, Zhen Ning, Zhi-Kun |
author_sort | Ding, Jia-Tong |
collection | PubMed |
description | Background: Colorectal cancers (CRCs) continue to be the leading cause of cancer-related deaths worldwide. The exact landscape of the molecular features of TGF-β pathway-inducing CRCs remains uncharacterized. Methods: Unsupervised hierarchical clustering was performed to stratify samples into two clusters based on the differences in TGF-β pathways. Weighted gene co-expression network analysis was applied to identify the key gene modules mediating the different characteristics between two subtypes. An algorithm integrating the least absolute shrinkage and selection operator (LASSO), XGBoost, and random forest regression was performed to narrow down the candidate genes. Further bioinformatic analyses were performed focusing on COMP-related immune infiltration and functions. Results: The integrated machine learning algorithm identified COMP as the hub gene, which exhibited a significant predictive value for two subtypes with an area under the curve (AUC) value equaling 0.91. Further bioinformatic analysis revealed that COMP was significantly upregulated in various cancers, especially in advanced CRCs, and regulated the immune infiltration, especially M2 macrophages and cancer-associated fibroblasts in CRCs. Conclusions: Comprehensive immune analysis and experimental validation demonstrate that COMP is a reliable signature for subtype prediction. Our results could provide a new point for TGFβ-targeted anticancer drugs and contribute to guiding clinical decision making for CRC patients. |
format | Online Article Text |
id | pubmed-9775768 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97757682022-12-23 TGF-β Pathways Stratify Colorectal Cancer into Two Subtypes with Distinct Cartilage Oligomeric Matrix Protein (COMP) Expression-Related Characteristics Ding, Jia-Tong Zhou, Hao-Nan Huang, Ying-Feng Peng, Jie Huang, Hao-Yu Yi, Hao Zong, Zhen Ning, Zhi-Kun Biomolecules Article Background: Colorectal cancers (CRCs) continue to be the leading cause of cancer-related deaths worldwide. The exact landscape of the molecular features of TGF-β pathway-inducing CRCs remains uncharacterized. Methods: Unsupervised hierarchical clustering was performed to stratify samples into two clusters based on the differences in TGF-β pathways. Weighted gene co-expression network analysis was applied to identify the key gene modules mediating the different characteristics between two subtypes. An algorithm integrating the least absolute shrinkage and selection operator (LASSO), XGBoost, and random forest regression was performed to narrow down the candidate genes. Further bioinformatic analyses were performed focusing on COMP-related immune infiltration and functions. Results: The integrated machine learning algorithm identified COMP as the hub gene, which exhibited a significant predictive value for two subtypes with an area under the curve (AUC) value equaling 0.91. Further bioinformatic analysis revealed that COMP was significantly upregulated in various cancers, especially in advanced CRCs, and regulated the immune infiltration, especially M2 macrophages and cancer-associated fibroblasts in CRCs. Conclusions: Comprehensive immune analysis and experimental validation demonstrate that COMP is a reliable signature for subtype prediction. Our results could provide a new point for TGFβ-targeted anticancer drugs and contribute to guiding clinical decision making for CRC patients. MDPI 2022-12-14 /pmc/articles/PMC9775768/ /pubmed/36551305 http://dx.doi.org/10.3390/biom12121877 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ding, Jia-Tong Zhou, Hao-Nan Huang, Ying-Feng Peng, Jie Huang, Hao-Yu Yi, Hao Zong, Zhen Ning, Zhi-Kun TGF-β Pathways Stratify Colorectal Cancer into Two Subtypes with Distinct Cartilage Oligomeric Matrix Protein (COMP) Expression-Related Characteristics |
title | TGF-β Pathways Stratify Colorectal Cancer into Two Subtypes with Distinct Cartilage Oligomeric Matrix Protein (COMP) Expression-Related Characteristics |
title_full | TGF-β Pathways Stratify Colorectal Cancer into Two Subtypes with Distinct Cartilage Oligomeric Matrix Protein (COMP) Expression-Related Characteristics |
title_fullStr | TGF-β Pathways Stratify Colorectal Cancer into Two Subtypes with Distinct Cartilage Oligomeric Matrix Protein (COMP) Expression-Related Characteristics |
title_full_unstemmed | TGF-β Pathways Stratify Colorectal Cancer into Two Subtypes with Distinct Cartilage Oligomeric Matrix Protein (COMP) Expression-Related Characteristics |
title_short | TGF-β Pathways Stratify Colorectal Cancer into Two Subtypes with Distinct Cartilage Oligomeric Matrix Protein (COMP) Expression-Related Characteristics |
title_sort | tgf-β pathways stratify colorectal cancer into two subtypes with distinct cartilage oligomeric matrix protein (comp) expression-related characteristics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9775768/ https://www.ncbi.nlm.nih.gov/pubmed/36551305 http://dx.doi.org/10.3390/biom12121877 |
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