Investigation of possible associations between tryptophan/kynurenine status and FOXP3 expression in colorectal cancer

Yükleniyor...
Küçük Resim

Tarih

2022

Dergi Başlığı

Dergi ISSN

Cilt Başlığı

Yayıncı

Taylor and Francis

Erişim Hakkı

info:eu-repo/semantics/closedAccess

Özet

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??mol/L, kynurenine level was 1.33?±?0.02??mol/L, and the kynurenic acid level was 0.01?±?0.001??mol/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.

Açıklama

Anahtar Kelimeler

PCR-RFLP, HPLC, Colorectal Cancer (CRC), Tryptophan Metabolis, Gene Expression

Kaynak

Scandinavian Journal of Clinical and Loboratory İnvestigation

WoS Q Değeri

Q4

Scopus Q Değeri

Q2

Cilt

82

Sayı

3

Künye

Ay EN, Demirkol Ş, Hakan MT, Horozoğlu C, Arıkan S, Doğan MB, Akyüz F, Hepokur CÖ, Yaylım İ. Investigation of possible associations between tryptophan/kynurenine status and FOXP3 expression in colorectal cancer. Scand J Clin Lab Invest. 2022 May;82(3):185-191. doi: 10.1080/00365513.2022.2040050. Epub 2022 Apr 22. PMID: 35452343.