Investigation of possible associations between tryptophan/kynurenine status and FOXP3 expression in colorectal cancer
View/ Open
Date
2022Author
Ay, Ebru NurDemirkol,Şeyda
Hakan,Mehmet Tolgahan
Horozoğlu,Cem
Arıkan,Soykan
Doğan,Mehmet Baki
Akyüz, Filiz
Özsoy Hepokur, Ceylan
Yaylım,İlhan
Metadata
Show full item recordAbstract
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 tran scription factor FOXP3 gene in colorectal cancer (CRC). Patients with CRC (n ¼ 159) and controls
(n ¼ 112) were included in the study. The FOXP3 rs3761548 variant genotyping from the isolated gen omic 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 lmol/L, kynurenine level was 1.33 ± 0.02 lmol/L, and the kynurenic acid level was
0.01 ± 0.001 lmol/L. The level of tryptophan was found to be low in CRC compared to control
(p < .001). In cases with CRC, CC genotype (p ¼ .048) and C allele (p ¼ .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 (T3þ T4) than in the early
tumor stage (T1þ T2) (p ¼ .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