c-Myb and its Effector COX-2 as an Indicator Associated with Prognosis and Therapeutic Outcome in Colorectal Cancer

Abstract

Background: One of our previous studies have demonstrated that the cancer suppressor miR-150 regulated the progression of colorectal cancer (CRC) by down-regulating v-myb avian myeloblastosis viral oncogene homolog (c-Myb). The purpose of present study was to evaluate the prognostic value of the expression of c-Myb and its effector, prostaglandin-endoperoxide synthase 2 (COX-2) in patients with CRC. Methods: We used tissue microarrays (containing 202 CRC tissues and matched adjacent normal tissues) and conducted immunohistochemical analysis and western blotting analysis (containing 3 CRC tissues and matched adjacent normal tissues) to detect the expression of c-Myb and COX-2. Results: Compared with the adjacent nontumorous tissues, both the expression levels of c-Myb and COX-2 were higher in the cancer tissues. A statistically significant correlation was found between the expression of c-Myb and COX-2. Elevated c-Myb and COX-2 were associated with more advanced tumor invasion and poorer overall survival by univariate analysis. Higher expression levels of both c-Myb and COX-2 were significantly associated with shorter overall survival for stage II and stage III patients with 5-Fu based chemotherapy. Multivariate analysis identified the lymph node involvement, distant metastatic spread and the elevated c-Myb and COX-2 as independent factors of poor prognosis for CRC. Conclusions: In conclusion, the overexpression of both c-Myb and COX-2 would be of prognostic screening value in patients with CRC.

The Inflammatory Profile of the Tumor Microenvironment, Orchestrated by Cyclooxygenase-2, Promotes Epithelial-Mesenchymal Transition

“…Besides, hypoxia promotes the inflammatory cytokine-induced c-Myb expression towards areas of the promoter-type I collagen gene ( COL1A2 ). This event could generate an excessive increase of the stromal component in the TME and promote hypoxic areas with high expression of HIF1-α ( 124 ). Therefore, we suggest to analyzing in detail the association between c-Myb expression and COX-2.…”