Cullin 4B is a novel prognostic marker that correlates with colon cancer progression and pathogenesis

Abstract

Cullin 4B (CUL4B), a scaffold protein of the Cullin4B-RING E3 ligase complex, functions in proteolysis. The present study aims to investigate its expression pattern and evaluate whether CUL4B expression was associated with histopathological and prognosis in the patients with colon cancer. Real-time PCR and western blot were used to identify CUL4B expression in tumor tissue and the paired adjacent normal mucosa from patients with colon cancer. Immunohistochemistry on a tissue microarray containing 203 cases of colon cancer was performed to analyze the association between CUL4B expression and clinicopathological features. Results indicated that CUL4B mRNA and protein levels in tumor tissues were both higher than that in normal mucosae (P < 0.001). Immunohistochemical study displayed that high CUL4B expression was significantly associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion, and advanced tumor stage. Patients with CUL4B-positive tumors had a higher recurrence rate and poorer survival than patients with CUL4B-negative tumors. In multivariate analyses, CUL4B expression was an independent factor for determining colon cancer prognosis after surgery. In conclusion, CUL4B might promote the progression of colon cancer and can be served as a novel independent prognostic marker for the prediction of recurrence in colon cancer.

The CUL4B/AKT/β-Catenin Axis Restricts the Accumulation of Myeloid-Derived Suppressor Cells to Prohibit the Establishment of a Tumor-Permissive Microenvironment

“…CUL4B has recently been shown to be highly expressed in a variety of human malignancy and is positively correlated with tumor progression (25,26,29,39,40). In the current study, we demonstrated that CUL4B functions to limit the expansion and activity of MDSCs that are an integral part of the immunosuppressive tumor microenvironment.…”

The role of cullin4B in human cancers

“…High expression of CUL4B expression was reported to be related to tumor histological differentiation, invasion, distant metastasis, tumor size, lymph node metastasis, overall and recurrence rate, as well as disease-free survival in breast, colorectal, cervical, oesophageal and lung cancers [3, 18, 20, 27]. Study has shown that knockdown CUL4B could suppress the epithelial–mesenchymal transition (EMT) progress [28].…”

Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B

“…In the colorectal epithelium, cells turn over quickly and are exposed to various DNA adduct-forming molecules found in charcoal, fried food, and cigarette smoke. Analysis of a large cohort of colorectal cancer patients in China showed that tumor cells have higher CUL4B expression than surrounding normal mucosal cells and that high CUL4B expression (both mRNA as well as protein) correlates with tumor invasiveness, metastasis, more advanced tumor stages and poorer prognosis (Jiang et al, 2013). Another study showed that CUL4B protein and transcript levels are higher in colorectal cancers (Hu et al, 2012).…”