Investigation of possible associations between tryptophan/kynurenine status and FOXP3 expression in colorectal cancer. (2nd May 2022)

• Record Type: Journal Article
• Authors: Ay, Ebru Nur; Demirkol, Şeyda; Hakan, Mehmet Tolgahan; Horozoğlu, Cem; Arıkan, Soykan; Doğan, Mehmet Baki; Akyüz, Filiz; Hepokur, Ceylan Özsoy; Yaylım, İlhan
• Is Part Of: Scandinavian journal of clinical & laboratory investigation. Volume 82:Number 3(2022)
• Page Start: 185
• Page End: 191
• Publication Date: 2022-05-02
• Subjects: Colorectal cancer (CRC) -- tryptophan metabolism -- PCR-RFLP -- gene expression -- HPLC; Clinical biochemistry -- Periodicals; Physiology, Pathological -- Periodicals; Physiology, Experimental -- Periodicals; Medicine -- Research -- Periodicals; Clinical medicine -- Periodicals; 616.0072
• DOI: 10.1080/00365513.2022.2040050
• Languages: English
• ISSNs: 0036-5513

Abstract

Abstract: Tryptophan metabolism in the tumor microenvironment exerts immunosuppressive effects by affecting the anti-tumor functions of immune cells. The immunosuppressive roles of tryptophan and tryptophan metabolites and their effects on the FOXP3 gene, highly expressed in regulatory T cells (Tregs), are remarkable. Our study aimed to investigate the relation between tryptophan metabolism and the transcription factor FOXP3 gene in colorectal cancer (CRC). Patients with CRC ( n = 159) and controls ( n = 112) were included in the study. The FOXP3 rs3761548 variant genotyping from the isolated genomic DNA was performed by PCR-RFLP. FOXP3 gene expression was determined by Q-PCR in RNAs isolated from resected tissues at the same time. Serum tryptophan, kynurenine, kynurenic acid levels of the cases were determined by HPLC. In serum samples with CRC, tryptophan level was 14.32 ± 1.09 μmol/L, kynurenine level was 1.33 ± 0.02 μmol/L, and the kynurenic acid level was 0.01 ± 0.001 μmol/L. The level of tryptophan was found to be low in CRC compared to control ( p < .001). In cases with CRC, CC genotype ( p = .048) and C allele ( p = .012) frequency for FOXP3 rs3761548 were higher than the control group. It was found that the expression level of the FOXP3 gene was approximately 44 times higher in the advanced tumor stage (T3 + T4) than in the early tumor stage (T1 + T2) ( p = .021). We suggest that there may be a possible relationship among serum TRP, TRP metabolites (KYN, KYNA) levels, FOXP3 gene expression, and FOXP3 gene variants in CRC pathogenesis.