Plasma Levels of Kynurenine, Soluble OX40 and Mir-138-5p Are Associated With Tumor-infiltrating Lymphocytes in Colorectal Cancer: An Exploratory Study

Zor D. S., Hakan M. T., Özgür E., Horozoglu C., Yörüker E. E., Kulle C. B., ...Daha Fazla

ANTICANCER RESEARCH, cilt.43, sa.7, ss.3281-3288, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 43 Sayı: 7
  • Basım Tarihi: 2023
  • Doi Numarası: 10.21873/anticanres.16503
  • Dergi Adı: ANTICANCER RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, Gender Studies Database, Veterinary Science Database
  • Sayfa Sayıları: ss.3281-3288
  • Anahtar Kelimeler: Colorectal cancer, kynurenine pathway, miR-138-5p, plasma, sOX40
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.