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Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy
Background: Chemotherapy is the basic treatment for colorectal cancer (CRC). However, colorectal cancer cells often develop resistance to chemotherapy drugs, leading to recurrence and poor prognosis. More and more studies have shown that the Homologous recombination (HR) pathway plays an important r...
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/PMC9207269/ https://www.ncbi.nlm.nih.gov/pubmed/35734400 http://dx.doi.org/10.3389/fphar.2022.920939 |
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author | Lin, Yan Liao, Xiaoli Zhang, Yumei Wu, Guobin Ye, Jiazhou Luo, Shanshan He, Xinxin Luo, Min Xie, Mingzhi Zhang, Jinyan Li, Qian Huang, Yu Liao, Sina Li, Yongqiang Liang, Rong |
author_facet | Lin, Yan Liao, Xiaoli Zhang, Yumei Wu, Guobin Ye, Jiazhou Luo, Shanshan He, Xinxin Luo, Min Xie, Mingzhi Zhang, Jinyan Li, Qian Huang, Yu Liao, Sina Li, Yongqiang Liang, Rong |
author_sort | Lin, Yan |
collection | PubMed |
description | Background: Chemotherapy is the basic treatment for colorectal cancer (CRC). However, colorectal cancer cells often develop resistance to chemotherapy drugs, leading to recurrence and poor prognosis. More and more studies have shown that the Homologous recombination (HR) pathway plays an important role in chemotherapy treatment for tumors. However, the relationship between HR pathway, chemotherapy sensitivity, and the prognosis of CRC patients is still unclear. Methods: We collected 35 samples of CRC patients after chemotherapy treatment from Guangxi Medical University Cancer Hospital, then collected mutation data and clinical prognosis data from the group. We also downloaded Mondaca-CRC, TCGA-CRC cohorts for chemotherapy treatment. Result: We found that HR mutant-type (HR-MUT) patients are less likely to experience tumor metastasis after receiving chemotherapy. Additionally, our univariate and multivariate cox regression models showed that HR-MUT can be used as an independent predictor of the prognosis of chemotherapy for CRC patients. The KM curve showed that patients with HR-MUT CRC had significantly prolonged overall survival (OS) time (log-rank p = 0.017; hazard ratio (HR) = 0.69). Compared to HR mutant-type (HR-WT), HR-MUT has a significantly lower IC50 value with several chemotherapeutic drugs. Pathway enrichment analysis further revealed that the HR-MUT displayed a significantly lower rate of DNA damage repair ability, tumor growth, metastasis activity, and tumor fatty acid metabolism activity than HR-WT, though its immune response activity was notably higher. Conclusion: These findings indicate that HR-MUT may be a relevant marker for CRC patients receiving chemotherapy, as it is closely related to improving OS time and reducing chemotherapy resistance. |
format | Online Article Text |
id | pubmed-9207269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92072692022-06-21 Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy Lin, Yan Liao, Xiaoli Zhang, Yumei Wu, Guobin Ye, Jiazhou Luo, Shanshan He, Xinxin Luo, Min Xie, Mingzhi Zhang, Jinyan Li, Qian Huang, Yu Liao, Sina Li, Yongqiang Liang, Rong Front Pharmacol Pharmacology Background: Chemotherapy is the basic treatment for colorectal cancer (CRC). However, colorectal cancer cells often develop resistance to chemotherapy drugs, leading to recurrence and poor prognosis. More and more studies have shown that the Homologous recombination (HR) pathway plays an important role in chemotherapy treatment for tumors. However, the relationship between HR pathway, chemotherapy sensitivity, and the prognosis of CRC patients is still unclear. Methods: We collected 35 samples of CRC patients after chemotherapy treatment from Guangxi Medical University Cancer Hospital, then collected mutation data and clinical prognosis data from the group. We also downloaded Mondaca-CRC, TCGA-CRC cohorts for chemotherapy treatment. Result: We found that HR mutant-type (HR-MUT) patients are less likely to experience tumor metastasis after receiving chemotherapy. Additionally, our univariate and multivariate cox regression models showed that HR-MUT can be used as an independent predictor of the prognosis of chemotherapy for CRC patients. The KM curve showed that patients with HR-MUT CRC had significantly prolonged overall survival (OS) time (log-rank p = 0.017; hazard ratio (HR) = 0.69). Compared to HR mutant-type (HR-WT), HR-MUT has a significantly lower IC50 value with several chemotherapeutic drugs. Pathway enrichment analysis further revealed that the HR-MUT displayed a significantly lower rate of DNA damage repair ability, tumor growth, metastasis activity, and tumor fatty acid metabolism activity than HR-WT, though its immune response activity was notably higher. Conclusion: These findings indicate that HR-MUT may be a relevant marker for CRC patients receiving chemotherapy, as it is closely related to improving OS time and reducing chemotherapy resistance. Frontiers Media S.A. 2022-06-06 /pmc/articles/PMC9207269/ /pubmed/35734400 http://dx.doi.org/10.3389/fphar.2022.920939 Text en Copyright © 2022 Lin, Liao, Zhang, Wu, Ye, Luo, He, Luo, Xie, Zhang, Li, Huang, Liao, Li and Liang. 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 | Pharmacology Lin, Yan Liao, Xiaoli Zhang, Yumei Wu, Guobin Ye, Jiazhou Luo, Shanshan He, Xinxin Luo, Min Xie, Mingzhi Zhang, Jinyan Li, Qian Huang, Yu Liao, Sina Li, Yongqiang Liang, Rong Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy |
title | Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy |
title_full | Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy |
title_fullStr | Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy |
title_full_unstemmed | Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy |
title_short | Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy |
title_sort | homologous recombination pathway alternation predicts prognosis of colorectal cancer with chemotherapy |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207269/ https://www.ncbi.nlm.nih.gov/pubmed/35734400 http://dx.doi.org/10.3389/fphar.2022.920939 |
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