Article ; Online: Plasma Levels of Kynurenine, Soluble OX40 and Mir-138-5p Are Associated With Tumor-infiltrating Lymphocytes in Colorectal Cancer: An Exploratory Study.
2023 Volume 43, Issue 7, Page(s) 3281–3288
Abstract: Background/aim: Colorectal cancer (CRC) is one of leading cancers in terms of incidence and mortality. Interaction of tumor cells with the surrounding microenvironment plays a crucial role in the development and progression of CRC. Many pathways such as ...
| Abstract | Background/aim: Colorectal cancer (CRC) is one of leading cancers in terms of incidence and mortality. Interaction of tumor cells with the surrounding microenvironment plays a crucial role in the development and progression of CRC. Many pathways such as the kynurenine pathway, OX40/OX40L-mediated signaling and microRNAs targeting PD-L1 may be involved in CRC development by affecting T cell activation, thus creating an immune-deficient microenvironment. Herein, our goal was to assess the association between plasma levels of tryptophan (TRP), kynurenine (KYN), KYN/TRP ratio, soluble OX40 (sOX40) and PD-L1-targeting miR-138-5p and CRC risk. Patients and methods: Plasma concentrations of TRP and KYN were determined by HPLC; sOX40 was measured by ELISA whereas circulating miR-138-5p was measured by quantitative PCR in pathologically confirmed CRC patients and colonoscopy-verified CRC-free controls without polyps (control group 1) and with polyps (control group 2). Results: We found significantly lower plasma levels of TRP in CRC patients compared to control groups which resulted in significantly higher KYN/TRP ratio in CRC patients than in the controls (p=0.007). Plasma levels of sOX40 did not significantly differ between groups. The levels of circulating miR-138-5p were significantly lower in CRC patients (relative median value 0.02) than in the control groups (relative median values 0.2 and 4.29, respectively) (p=0.03). Plasma levels of KYN and sOX40 were considerably higher in patients with no tumor-infiltrating lymphocytes (TILs) than those with TILs whereas circulating miR-138-5p had opposite expression pattern in plasma. Conclusion: The kynurenine pathway and miR-138-5p are associated with CRC risk and plasma levels of KYN, sOX40 and miR-138-5p are related to TILs, making them possible target molecules in possible immunotherapeutic targets for CRC. |
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| MeSH term(s) | Humans ; Kynurenine ; B7-H1 Antigen ; MicroRNAs/metabolism ; Tryptophan ; Colorectal Neoplasms ; Lymphocytes/pathology ; Tumor Microenvironment | |||||
| Chemical Substances | Kynurenine (343-65-7) ; B7-H1 Antigen ; MicroRNAs ; Tryptophan (8DUH1N11BX) ; MIRN138 microRNA, human | |||||
| Language | English | |||||
| Publishing date | 2023-06-23 | |||||
| Publishing country | Greece | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 604549-2 | |||||
| ISSN | 1791-7530 ; 0250-7005 | |||||
| ISSN (online) | 1791-7530 | |||||
| ISSN | 0250-7005 | |||||
| DOI | 10.21873/anticanres.16503 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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