T helper 17 (Th17) and T regulatory (Treg) cytokines appear to be contributing greatly to colorectal cancer
(CRC) development and progression. The aim of the current
study was to investigate the expression of Foxp3; IL10;
TGFB1; IL17A; IL6 and NOS2 genes in tumor tissue, regional
positive lymph nodes and distant metastasis obtained from 26
patients with advanced CRC. Quantitative real-time polymerase chain reaction (qPCR) was performed for mRNA detection
by TaqMan gene expression assay. In distant metastasis, IL6
was strongly expressed, over 7.5 fold, followed by Tregrelated genes Foxp3; IL10 and TGFB1 in contrast to IL17A
and NOS2. The similar pattern of expression was observed in
positive regional lymph node in addition to significant downregulation of NOS2 (RQ = 0.287; p = 0.011) and a trend for the
elevation of IL17A. In tumor tissue, Fopx3 was significantly
upregulated and Foxp3 mRNA positively correlated with
TGFB1 in all investigated tissue types. In tumor tissue, expression of IL17A was correlated with NOS2 (r = 0.68; p = 0.005),
while in distant metastasis IL10 was in strong relation with
TGFB1 and IL6. In addition, a reverse correlation between
IL6 and NOS2 (r = −0.66; p = 0.009), was observed in distant
metastasis. The simultaneous expression of given Treg and
Th17-related genes found both in the primary tumor and in
the regional lymph nodes appears to provide suitable microenvironment sufficient for promoting metastatic growth. The upregulation of Foxp3; IL10, TGFB1 and IL6 might be a transcriptional profile hallmark for colorectal metastases.

• Upregulation of Treg-Related Genes in Addition with IL6 Showed the Significant Role for the Distant Metastasis in Colorectal Cancer