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Screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer

Background: Colon cancer is one of the most common malignant tumors in the world. FOLFIRI (leucovorin, fluorouracil, and irinotecan) is a common combination in chemotherapy regimens. However, insensitivity to FOLFIRI is an important factor in the effectiveness of the treatment for advanced colon can...

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Autores principales: Wu, Pingping, Pan, Xuan, Lu, Kecen, Gu, Ning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745058/
https://www.ncbi.nlm.nih.gov/pubmed/36523769
http://dx.doi.org/10.3389/fgene.2022.928356
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author Wu, Pingping
Pan, Xuan
Lu, Kecen
Gu, Ning
author_facet Wu, Pingping
Pan, Xuan
Lu, Kecen
Gu, Ning
author_sort Wu, Pingping
collection PubMed
description Background: Colon cancer is one of the most common malignant tumors in the world. FOLFIRI (leucovorin, fluorouracil, and irinotecan) is a common combination in chemotherapy regimens. However, insensitivity to FOLFIRI is an important factor in the effectiveness of the treatment for advanced colon cancer. Our study aimed to explore precise molecular targets associated with chemotherapy responses in colon cancer. Methods: Gene expression profiles of 21 patients with advanced colorectal cancer who received chemotherapy based on FOLFIRI were obtained from the Gene Expression Omnibus (GEO) database. The gene co-expression network was constructed by the weighted gene co-expression network analysis (WGCNA) and functional gene modules were screened out. Clinical phenotypic correlation analysis was used to identify key gene modules. Gene Ontology and pathway enrichment analysis were used to screen enriched genes in key modules. Protein–protein interaction (PPI) analysis was used to screen out key node genes. Based on the Gene Expression Profiling Interactive Analysis (GEPIA) database, the correlation between the expression levels of these genes and the overall survival (OS) and disease-free survival (DFS) of colon cancer patients was investigated, and the hub genes were screened out. Immunohistochemistry of candidate hub genes was identified using the Human Protein Atlas database. Finally, clinical information and RNA sequencing data of colon cancer were obtained from The Cancer Genome Atlas project database (TCGA), the GEPIA, and the Human Atlas databases for validation. Results: The WGCNA revealed that three hub genes were closely related to chemotherapy insensitivity of colon cancer: AEBP1, BGN, and TAGLN. The protein expression levels of AEBP1, BGN, and TAGLN in tumor tissues were higher than those in normal tissues. In addition, the gene expression levels of AEBP1, BGN, and TAGLN were negatively correlated with OS and DFS in colon cancer patients. Therefore, AEBP1, BGN, and TAGLN have been identified as potential biomarkers related to the response to FOLFIRI treatment of colon cancer. Conclusion: We found that AEBP1, BGN, and TAGLN, as potential predictive biomarkers, may play an important role in the response to FOLFIRI treatment of colon cancer and as a precise molecular target associated with chemotherapy response in colon cancer.
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spelling pubmed-97450582022-12-14 Screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer Wu, Pingping Pan, Xuan Lu, Kecen Gu, Ning Front Genet Genetics Background: Colon cancer is one of the most common malignant tumors in the world. FOLFIRI (leucovorin, fluorouracil, and irinotecan) is a common combination in chemotherapy regimens. However, insensitivity to FOLFIRI is an important factor in the effectiveness of the treatment for advanced colon cancer. Our study aimed to explore precise molecular targets associated with chemotherapy responses in colon cancer. Methods: Gene expression profiles of 21 patients with advanced colorectal cancer who received chemotherapy based on FOLFIRI were obtained from the Gene Expression Omnibus (GEO) database. The gene co-expression network was constructed by the weighted gene co-expression network analysis (WGCNA) and functional gene modules were screened out. Clinical phenotypic correlation analysis was used to identify key gene modules. Gene Ontology and pathway enrichment analysis were used to screen enriched genes in key modules. Protein–protein interaction (PPI) analysis was used to screen out key node genes. Based on the Gene Expression Profiling Interactive Analysis (GEPIA) database, the correlation between the expression levels of these genes and the overall survival (OS) and disease-free survival (DFS) of colon cancer patients was investigated, and the hub genes were screened out. Immunohistochemistry of candidate hub genes was identified using the Human Protein Atlas database. Finally, clinical information and RNA sequencing data of colon cancer were obtained from The Cancer Genome Atlas project database (TCGA), the GEPIA, and the Human Atlas databases for validation. Results: The WGCNA revealed that three hub genes were closely related to chemotherapy insensitivity of colon cancer: AEBP1, BGN, and TAGLN. The protein expression levels of AEBP1, BGN, and TAGLN in tumor tissues were higher than those in normal tissues. In addition, the gene expression levels of AEBP1, BGN, and TAGLN were negatively correlated with OS and DFS in colon cancer patients. Therefore, AEBP1, BGN, and TAGLN have been identified as potential biomarkers related to the response to FOLFIRI treatment of colon cancer. Conclusion: We found that AEBP1, BGN, and TAGLN, as potential predictive biomarkers, may play an important role in the response to FOLFIRI treatment of colon cancer and as a precise molecular target associated with chemotherapy response in colon cancer. Frontiers Media S.A. 2022-11-29 /pmc/articles/PMC9745058/ /pubmed/36523769 http://dx.doi.org/10.3389/fgene.2022.928356 Text en Copyright © 2022 Wu, Pan, Lu and Gu. 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
Wu, Pingping
Pan, Xuan
Lu, Kecen
Gu, Ning
Screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer
title Screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer
title_full Screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer
title_fullStr Screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer
title_full_unstemmed Screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer
title_short Screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer
title_sort screening prognostic genes related to leucovorin, fluorouracil, and irinotecan treatment sensitivity by performing co-expression network analysis for colon cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745058/
https://www.ncbi.nlm.nih.gov/pubmed/36523769
http://dx.doi.org/10.3389/fgene.2022.928356
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