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Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies and its incidence and mortality are increasing yearly. 5-Fluorouracil (5-FU) has long been used as a standard first-line treatment for CRC patients. Although 5-FU-based chemotherapy is effective for advanced CRC, the conseque...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247273/ https://www.ncbi.nlm.nih.gov/pubmed/35784334 http://dx.doi.org/10.3389/fimmu.2022.887048 |
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author | Huang, Xingxing Ke, Kun Jin, Weiwei Zhu, Qianru Zhu, Qicong Mei, Ruyi Zhang, Ruonan Yu, Shuxian Shou, Lan Sun, Xueni Feng, Jiao Duan, Ting Mou, Yiping Xie, Tian Wu, Qibiao Sui, Xinbing |
author_facet | Huang, Xingxing Ke, Kun Jin, Weiwei Zhu, Qianru Zhu, Qicong Mei, Ruyi Zhang, Ruonan Yu, Shuxian Shou, Lan Sun, Xueni Feng, Jiao Duan, Ting Mou, Yiping Xie, Tian Wu, Qibiao Sui, Xinbing |
author_sort | Huang, Xingxing |
collection | PubMed |
description | BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies and its incidence and mortality are increasing yearly. 5-Fluorouracil (5-FU) has long been used as a standard first-line treatment for CRC patients. Although 5-FU-based chemotherapy is effective for advanced CRC, the consequent resistance remains a key problem and causes the poor prognosis of CRC patients. Thus, there is an urgent need to identify new biomarkers to predict the response to 5-FU-based chemotherapy. METHODS: CRC samples were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The immune-related genes were retrieved from the ImmPort database. Single-cell sequencing results from colorectal cancer were obtained by the ArrayExpress database. 5-FU resistance-related genes were filtered and validated by R packages. ESTIMATE algorithms were used to assess the tumor microenvironment (TME). KEGG and GO analysis were performed to explore the biological signaling pathway for resistant-response patients and sensitive-response patients in the tumor microenvironment. pRRophetic algorithms were used to predict 5-FU sensitivity. GSEA and GSVA analysis was performed to excavate the biological signaling pathway of the RBP7 gene. RESULTS: Nine immune-related genes were identified to be associated with 5-FU resistance and poor disease-free survival (DFS) of CRC patients and the signature of these genes was developed in a DFS-prognostic model. Four immune-related genes were determined to be associated with 5-FU resistance and overall survival (OS) of CRC patients. The signature of these genes was developed an OS-prognostic model. ESTIMATE scores showed a significant difference between 5-FU resistant and 5-FU sensitive CRC patients. Resistant-response patients and sensitive-response patients to 5-FU based chemotherapy showed different GO and KEGG enrichment on the tumor microenvironment. RBP7, as a tumor immune microenvironment (TIME) related gene, was found to have the potential of predicting chemotherapy resistance and poor prognosis of CRC patients. GSEA analysis showed multiple signaling differences between the high and low expression of RBP7 in CRC patients. Hypoxia and TNFα signaling via NFκB gene sets were significantly different between chemotherapy resistant (RBP7(High)) and chemotherapy sensitive (RBP7(Low)) patients. Single-cell RNA-seq suggested RBP7 was centrally distributed in endothelial stalk cells, endothelial tip cells, and myeloid cells. CONCLUSIONS: Immune-related genes will hopefully be potential prognostic biomarkers to predict chemotherapy resistance for CRC. RBP7 may function as a tumor microenvironment regulator to induce 5-FU resistance, thereby affecting the prognosis of CRC patients. |
format | Online Article Text |
id | pubmed-9247273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92472732022-07-02 Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer Huang, Xingxing Ke, Kun Jin, Weiwei Zhu, Qianru Zhu, Qicong Mei, Ruyi Zhang, Ruonan Yu, Shuxian Shou, Lan Sun, Xueni Feng, Jiao Duan, Ting Mou, Yiping Xie, Tian Wu, Qibiao Sui, Xinbing Front Immunol Immunology BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies and its incidence and mortality are increasing yearly. 5-Fluorouracil (5-FU) has long been used as a standard first-line treatment for CRC patients. Although 5-FU-based chemotherapy is effective for advanced CRC, the consequent resistance remains a key problem and causes the poor prognosis of CRC patients. Thus, there is an urgent need to identify new biomarkers to predict the response to 5-FU-based chemotherapy. METHODS: CRC samples were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The immune-related genes were retrieved from the ImmPort database. Single-cell sequencing results from colorectal cancer were obtained by the ArrayExpress database. 5-FU resistance-related genes were filtered and validated by R packages. ESTIMATE algorithms were used to assess the tumor microenvironment (TME). KEGG and GO analysis were performed to explore the biological signaling pathway for resistant-response patients and sensitive-response patients in the tumor microenvironment. pRRophetic algorithms were used to predict 5-FU sensitivity. GSEA and GSVA analysis was performed to excavate the biological signaling pathway of the RBP7 gene. RESULTS: Nine immune-related genes were identified to be associated with 5-FU resistance and poor disease-free survival (DFS) of CRC patients and the signature of these genes was developed in a DFS-prognostic model. Four immune-related genes were determined to be associated with 5-FU resistance and overall survival (OS) of CRC patients. The signature of these genes was developed an OS-prognostic model. ESTIMATE scores showed a significant difference between 5-FU resistant and 5-FU sensitive CRC patients. Resistant-response patients and sensitive-response patients to 5-FU based chemotherapy showed different GO and KEGG enrichment on the tumor microenvironment. RBP7, as a tumor immune microenvironment (TIME) related gene, was found to have the potential of predicting chemotherapy resistance and poor prognosis of CRC patients. GSEA analysis showed multiple signaling differences between the high and low expression of RBP7 in CRC patients. Hypoxia and TNFα signaling via NFκB gene sets were significantly different between chemotherapy resistant (RBP7(High)) and chemotherapy sensitive (RBP7(Low)) patients. Single-cell RNA-seq suggested RBP7 was centrally distributed in endothelial stalk cells, endothelial tip cells, and myeloid cells. CONCLUSIONS: Immune-related genes will hopefully be potential prognostic biomarkers to predict chemotherapy resistance for CRC. RBP7 may function as a tumor microenvironment regulator to induce 5-FU resistance, thereby affecting the prognosis of CRC patients. Frontiers Media S.A. 2022-06-17 /pmc/articles/PMC9247273/ /pubmed/35784334 http://dx.doi.org/10.3389/fimmu.2022.887048 Text en Copyright © 2022 Huang, Ke, Jin, Zhu, Zhu, Mei, Zhang, Yu, Shou, Sun, Feng, Duan, Mou, Xie, Wu and Sui 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 | Immunology Huang, Xingxing Ke, Kun Jin, Weiwei Zhu, Qianru Zhu, Qicong Mei, Ruyi Zhang, Ruonan Yu, Shuxian Shou, Lan Sun, Xueni Feng, Jiao Duan, Ting Mou, Yiping Xie, Tian Wu, Qibiao Sui, Xinbing Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer |
title | Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer |
title_full | Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer |
title_fullStr | Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer |
title_full_unstemmed | Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer |
title_short | Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer |
title_sort | identification of genes related to 5-fluorouracil based chemotherapy for colorectal cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247273/ https://www.ncbi.nlm.nih.gov/pubmed/35784334 http://dx.doi.org/10.3389/fimmu.2022.887048 |
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