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

AbstractT 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 ofFoxp3;IL10;TGFB1;IL17A;IL6 andNOS2 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 Treg-related genesFoxp3;IL10 andTGFB1 in contrast toIL17A andNOS2. The similar pattern of expression was observed in positive regional lymph node in addition to significant down-regulation ofNOS2 (RQ  = 0.287;p = 0.011) and a trend for the elevation ofIL17A. In tumor tissue, Fopx3 was significantly upregulated andFoxp3 mRNA positively correlated withTGFB1 in all investigated tissue types. In tumor tissue, expression ofIL17A was correlated withNOS2 (r = 0.68;p = 0.005), while in distant metastasisIL10 was in strong relation withTGFB1 andIL6. In addition, a reverse correlation betweenIL6 andNOS2 (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 ofFoxp3;IL10,TGFB1 a...
Source: Cancer Microenvironment - Category: Cancer & Oncology Source Type: research