Autoinducer-2 of gut microbiota, a potential novel marker for human colorectal cancer, is associated with the activation of TNFSF9 signaling in macrophages
Objectives: The interaction between the quorum sensing (QS) molecules of gut microbiota and the immunity of colorectal cancer (CRC) has not been investigated before. Methods: We measured the concentration of autoinducer-2 (AI-2) in samples of stool, colorectal tissue, saliva and serum of CRC patient...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-10-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2019.1626192 |
| _version_ | 1830402364727623680 |
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| author | Qing Li Wei Peng Jiao Wu Xianfei Wang Yixing Ren Huan Li Yan Peng Xiaowei Tang Xiangsheng Fu |
| author_facet | Qing Li Wei Peng Jiao Wu Xianfei Wang Yixing Ren Huan Li Yan Peng Xiaowei Tang Xiangsheng Fu |
| author_sort | Qing Li |
| collection | DOAJ |
| description | Objectives: The interaction between the quorum sensing (QS) molecules of gut microbiota and the immunity of colorectal cancer (CRC) has not been investigated before. Methods: We measured the concentration of autoinducer-2 (AI-2) in samples of stool, colorectal tissue, saliva and serum of CRC patients, and compared this to AI-2 levels in colorectal adenoma (AD) and normal colon mucosa (NC). To explore the activated signaling pathways involved, we utilized AI-2 extracted from Fusobacterium nucleatum to stimulate macrophages and validated these in vitro findings in human CRC tissues. Results: The AI-2 concentration in both colorectal tissue and stool of CRC patients was significantly higher when compared to that in AD and NC (all P values < .01). The AI-2 concentration along with the progression of CRC in both tissues and stools was significantly increased (P= .045，P= .0003, respectively). After AI-2 stimulation, TNFSF9 was the most significantly increased protein in macrophage cells (P < .01). TNFSF9 expression was significantly higher in CRC tissues when compared to NCs (P< .0001), which was mainly derived from macrophages in the tumor microenvironment. Moreover, AI-2 level was positively associated with CD3 + T cell numbers (P= .0462), and negatively associated with CD4/CD8 ratio (P= .0113) within CRC tissues. Conclusions: We demonstrated for the first time that AI-2 may serve as a novel marker for screening CRC in the clinic. AI-2 was associated with tumor immunity in CRCs through tumor-associated macrophages and CD4/CD8 ratio in a TNFSF9-dependent manner. |
| first_indexed | 2024-12-20T16:52:46Z |
| format | Article |
| id | doaj.art-9c07f88c238f4e68a100309ca2dff605 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-20T16:52:46Z |
| publishDate | 2019-10-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-9c07f88c238f4e68a100309ca2dff6052022-12-21T19:32:48ZengTaylor & Francis GroupOncoImmunology2162-402X2019-10-0181010.1080/2162402X.2019.16261921626192Autoinducer-2 of gut microbiota, a potential novel marker for human colorectal cancer, is associated with the activation of TNFSF9 signaling in macrophagesQing Li0Wei Peng1Jiao Wu2Xianfei Wang3Yixing Ren4Huan Li5Yan Peng6Xiaowei Tang7Xiangsheng Fu8The Affiliated Hospital of Southwest Medical UniversityThe Affiliated Hospital of Southwest Medical UniversityThe Affiliated Hospital of Southwest Medical UniversityThe Second Affiliated Hospital of North Sichuan Medical CollegeThe Affiliated Hospital of North Sichuan Medical CollegeThe Affiliated Hospital of Southwest Medical UniversityThe Affiliated Hospital of Southwest Medical UniversityThe Affiliated Hospital of Southwest Medical UniversityThe Affiliated Hospital of North Sichuan Medical CollegeObjectives: The interaction between the quorum sensing (QS) molecules of gut microbiota and the immunity of colorectal cancer (CRC) has not been investigated before. Methods: We measured the concentration of autoinducer-2 (AI-2) in samples of stool, colorectal tissue, saliva and serum of CRC patients, and compared this to AI-2 levels in colorectal adenoma (AD) and normal colon mucosa (NC). To explore the activated signaling pathways involved, we utilized AI-2 extracted from Fusobacterium nucleatum to stimulate macrophages and validated these in vitro findings in human CRC tissues. Results: The AI-2 concentration in both colorectal tissue and stool of CRC patients was significantly higher when compared to that in AD and NC (all P values < .01). The AI-2 concentration along with the progression of CRC in both tissues and stools was significantly increased (P= .045，P= .0003, respectively). After AI-2 stimulation, TNFSF9 was the most significantly increased protein in macrophage cells (P < .01). TNFSF9 expression was significantly higher in CRC tissues when compared to NCs (P< .0001), which was mainly derived from macrophages in the tumor microenvironment. Moreover, AI-2 level was positively associated with CD3 + T cell numbers (P= .0462), and negatively associated with CD4/CD8 ratio (P= .0113) within CRC tissues. Conclusions: We demonstrated for the first time that AI-2 may serve as a novel marker for screening CRC in the clinic. AI-2 was associated with tumor immunity in CRCs through tumor-associated macrophages and CD4/CD8 ratio in a TNFSF9-dependent manner.http://dx.doi.org/10.1080/2162402X.2019.1626192autoinducer-2gut microbiotafusobacterium nucleatummacrophagescolorectal cancerimmune |
| spellingShingle | Qing Li Wei Peng Jiao Wu Xianfei Wang Yixing Ren Huan Li Yan Peng Xiaowei Tang Xiangsheng Fu Autoinducer-2 of gut microbiota, a potential novel marker for human colorectal cancer, is associated with the activation of TNFSF9 signaling in macrophages OncoImmunology autoinducer-2 gut microbiota fusobacterium nucleatum macrophages colorectal cancer immune |
| title | Autoinducer-2 of gut microbiota, a potential novel marker for human colorectal cancer, is associated with the activation of TNFSF9 signaling in macrophages |
| title_full | Autoinducer-2 of gut microbiota, a potential novel marker for human colorectal cancer, is associated with the activation of TNFSF9 signaling in macrophages |
| title_fullStr | Autoinducer-2 of gut microbiota, a potential novel marker for human colorectal cancer, is associated with the activation of TNFSF9 signaling in macrophages |
| title_full_unstemmed | Autoinducer-2 of gut microbiota, a potential novel marker for human colorectal cancer, is associated with the activation of TNFSF9 signaling in macrophages |
| title_short | Autoinducer-2 of gut microbiota, a potential novel marker for human colorectal cancer, is associated with the activation of TNFSF9 signaling in macrophages |
| title_sort | autoinducer 2 of gut microbiota a potential novel marker for human colorectal cancer is associated with the activation of tnfsf9 signaling in macrophages |
| topic | autoinducer-2 gut microbiota fusobacterium nucleatum macrophages colorectal cancer immune |
| url | http://dx.doi.org/10.1080/2162402X.2019.1626192 |
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