Differential profile of protumor immunological factors between the tumor site and the tumor-free site - predictive potential of IL-8 and COX2 for colorectal cancer and metastasis

Abstract

To study the role of host immune surveillance in the initiation and progression of colorectal cancer (CRC), a set of protumor immunological factors was determined by quantitative real-time PCR (q-PCR) between the primary tumor and the adjacent tumor-free site tissues in 63 patients with colorectal neoplasms. Results showed that expression levels of interleukin (IL)-1β, IL-6, IL-8, IL-17A, IL-23, and cyclooxygenase 2 (COX2) mRNAs, except transforming growth factor beta (TGFβ), in adenoma tissues were significantly higher than that in relative adjacent tissues. Difference of immunological factor levels between adenoma and adjacent tissues (Δ values) was in an order of ΔIL-8 > ΔIL-6 > ΔIL-17A > ΔIL-1β > ΔCOX2 > ΔIL-23; Analysis showed that the value of ΔCOX2 correlated to the grade of dysplastic degree in patients with adenoma. Notably, levels of all these immunological factors in CRC tissues were continuously increased, the order of values of Δ immunological factors was ΔIL-8 > ΔCOX2 > ΔIL-6 > ΔIL-1β > ΔIL-17A > ΔIL-23 > ΔTGFβ. Further analysis revealed that increased value of Δ IL-1β was associated with advanced TNM stage, a higher value of Δ COX2 tended to predicate a deeper degree of tumor invasion; and higher values of Δ IL-1β, IL-6 and COX2 closely correlated to lymph node metastasis in patients with CRC. In addition, the ratio of ΔIL-8/ΔTGFβ was most obvious changed factor and associated with node metastasis in patients with CRC. Therefore, we concluded that the difference of protumor immunological factor levels between the primary tumor site and tumor-free site along the adenoma-carcinoma sequence reflects the change of protumor/antitumor force balance, which is associated with CRC initiation and invasion.

Keywords: COX2; Colorectal cancer; Immunological factors; Interleukin; Metastasis.