Impacts of pre‐existing diabetes mellitus on colorectal cancer in a mice model

Abstract Background Although diabetes mellitus (DM) is regarded as a risk factor of colorectal cancer (CRC), the impacts of pre‐existing DM on CRC without drug intervention remain unknown. The purpose of this study was to investigate and analyze the effects of diabetes mellitus (DM) on colorectal ca...

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Main Authors: Yangbo Lv, Shuiquan Lin, Mingsheng Liu, Lihui Wang, Xiaoyu Wang, Li Cui, Jianguang Xu
Format: Article
Language:English
Published: Wiley 2023-05-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.5868
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author Yangbo Lv
Shuiquan Lin
Mingsheng Liu
Lihui Wang
Xiaoyu Wang
Li Cui
Jianguang Xu
author_facet Yangbo Lv
Shuiquan Lin
Mingsheng Liu
Lihui Wang
Xiaoyu Wang
Li Cui
Jianguang Xu
author_sort Yangbo Lv
collection DOAJ
description Abstract Background Although diabetes mellitus (DM) is regarded as a risk factor of colorectal cancer (CRC), the impacts of pre‐existing DM on CRC without drug intervention remain unknown. The purpose of this study was to investigate and analyze the effects of diabetes mellitus (DM) on colorectal cancer (CRC). And, to further explore the influencing factors and the mechanisms of DM affects CRC progression. Methods In this study, we investigated the effects of DM on CRC progression in a streptozotocin‐induced DM mice model. Furthermore, we evaluated the change of T cells levels using flow cytometry and indirect immunofluorescence. We assessed the alternation of gut microbiome and the transcriptional response using 16s rRNA sequencing and RNA‐seq. Results Results showed that the mice survival time was significantly decreased in CRC complicated with DM group (DM‐CRC), compared with only tumor bearing mice (CRC group). Furthermore, we found that DM could affect the immune response by changing the infiltration of CD4+ T cells, CD8+ T cells and mucosal‐associated invariant T cell (MAIT) in the CRC progression. In addition, DM could induce gut microbiome dysbiosis and change the transcriptional response in CRC complicated with DM. Conclusion For the first time, the effects of DM on CRC were systematically characterized in a mice model. Our findings highlight the effects of pre‐existing DM on CRC, and these findings should facilitate further studies in exploring and developing potentially targeted therapy for CRC in diabetic patients. Our results suggest that the effects induced by DM should be considered in the treatment for CRC complicated with DM patients.
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spelling doaj.art-94bd8cd02cbc44f78dd65178b47609512023-06-06T07:30:47ZengWileyCancer Medicine2045-76342023-05-011210116411165010.1002/cam4.5868Impacts of pre‐existing diabetes mellitus on colorectal cancer in a mice modelYangbo Lv0Shuiquan Lin1Mingsheng Liu2Lihui Wang3Xiaoyu Wang4Li Cui5Jianguang Xu6Department of Colorectal Surgery The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital Zhejiang Quzhou ChinaDepartment of Colorectal Surgery The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital Zhejiang Quzhou ChinaDepartment of Colorectal Surgery The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital Zhejiang Quzhou ChinaDepartment of Colorectal Surgery The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital Zhejiang Quzhou ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology Shanghai Jiao Tong University Shanghai ChinaShanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology Shanghai Jiao Tong University Shanghai ChinaDepartment of Gastroenterology The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital Zhejiang Quzhou ChinaAbstract Background Although diabetes mellitus (DM) is regarded as a risk factor of colorectal cancer (CRC), the impacts of pre‐existing DM on CRC without drug intervention remain unknown. The purpose of this study was to investigate and analyze the effects of diabetes mellitus (DM) on colorectal cancer (CRC). And, to further explore the influencing factors and the mechanisms of DM affects CRC progression. Methods In this study, we investigated the effects of DM on CRC progression in a streptozotocin‐induced DM mice model. Furthermore, we evaluated the change of T cells levels using flow cytometry and indirect immunofluorescence. We assessed the alternation of gut microbiome and the transcriptional response using 16s rRNA sequencing and RNA‐seq. Results Results showed that the mice survival time was significantly decreased in CRC complicated with DM group (DM‐CRC), compared with only tumor bearing mice (CRC group). Furthermore, we found that DM could affect the immune response by changing the infiltration of CD4+ T cells, CD8+ T cells and mucosal‐associated invariant T cell (MAIT) in the CRC progression. In addition, DM could induce gut microbiome dysbiosis and change the transcriptional response in CRC complicated with DM. Conclusion For the first time, the effects of DM on CRC were systematically characterized in a mice model. Our findings highlight the effects of pre‐existing DM on CRC, and these findings should facilitate further studies in exploring and developing potentially targeted therapy for CRC in diabetic patients. Our results suggest that the effects induced by DM should be considered in the treatment for CRC complicated with DM patients.https://doi.org/10.1002/cam4.5868colorectal cancerdiabetes mellitusgut microbiotaT‐cell infiltrationtranscriptome
spellingShingle Yangbo Lv
Shuiquan Lin
Mingsheng Liu
Lihui Wang
Xiaoyu Wang
Li Cui
Jianguang Xu
Impacts of pre‐existing diabetes mellitus on colorectal cancer in a mice model
Cancer Medicine
colorectal cancer
diabetes mellitus
gut microbiota
T‐cell infiltration
transcriptome
title Impacts of pre‐existing diabetes mellitus on colorectal cancer in a mice model
title_full Impacts of pre‐existing diabetes mellitus on colorectal cancer in a mice model
title_fullStr Impacts of pre‐existing diabetes mellitus on colorectal cancer in a mice model
title_full_unstemmed Impacts of pre‐existing diabetes mellitus on colorectal cancer in a mice model
title_short Impacts of pre‐existing diabetes mellitus on colorectal cancer in a mice model
title_sort impacts of pre existing diabetes mellitus on colorectal cancer in a mice model
topic colorectal cancer
diabetes mellitus
gut microbiota
T‐cell infiltration
transcriptome
url https://doi.org/10.1002/cam4.5868
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AT lihuiwang impactsofpreexistingdiabetesmellitusoncolorectalcancerinamicemodel
AT xiaoyuwang impactsofpreexistingdiabetesmellitusoncolorectalcancerinamicemodel
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