Cullin 4B is a novel prognostic marker that correlates with colon cancer progression and pathogenesis
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ORIGINAL PAPER
Cullin 4B is a novel prognostic marker that correlates with colon cancer progression and pathogenesis Tao Jiang • Hua-mei Tang • Ze-hua Wu Jian Chen • Su Lu • Chong-zhi Zhou • Dong-wang Yan • Zhi-hai Peng
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Received: 24 January 2013 / Accepted: 3 March 2013 / Published online: 7 May 2013 Ó Springer Science+Business Media New York 2013
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 Tao Jiang and Huamei Tang contributed equally to this work. T. Jiang Z. Wu J. Chen C. Zhou D. Yan (&) Z. Peng (&) Department of General Surgery, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080, People’s Republic of China e-mail: [email protected] Z. Peng e-mail: [email protected] H. Tang S. Lu Department of Pathology, Shanghai Jiaotong University Affiliated First People’s Hospital, 85 Wujin Road, Shanghai 200080, People’s Republic of China
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. Keywords Cullin 4B Colon cancer Prognosis Immunohistochemistry
Introduction Colon cancer is a major cause of cancer morbidity and mortality worldwide, and its incidence is keeping growing [1, 2]. In China, due to the inherited and somatic mutations factors, and the lifestyle changes, the risk of colon cancer significantly increased in 50 years, and the morbidity has the youth-oriented tendency [3, 4]. Currently, the main therapies for colon cancer are curative strategies such as colon resection, chemotherapy, and radiotherapy. However, the long-term outcome of colon cancer patients remains unsatisfactory due to the high recurrence rates and distant metastases. Molecular genetics have revealed that the occurrence of colon cancer is a series of molecular
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