CUL4B在结肠癌组织的表达及意义

The Expression of Cullin 4B and Its Significance in Patients with Colon Cancer

目的探讨Cullin-4B(CUL4B)基因在结肠癌组织中的表达及其与患者临床病理学特征间的相关性。方法在203例结肠癌组织芯片中,运用免疫组织化学检测CUL4B在结肠癌组织和配对癌旁组织中的表达情况,并分析其与结肠癌临床病理学指标之间的相关性;运用Western blot检测CUL4B在4例新鲜冰冻结肠癌及配对癌旁组织黏膜中的表达,比较其差异。结果结肠癌组织芯片结果显示:CUL4B主要表达于细胞核中;203例配对癌旁组织中CUL4B阴性表达188例(92.61%),弱阳性13例(6.4%),强阳性2例(0.99%);203例结肠癌组织中CUL4B阴性表达87例(42.86%),弱阳性45例(22.17%),强阳性71例(34.97%),CUL4B在结肠癌组织中的表达阳性率高于配对的癌旁组织(P<0.01)。Western blot结果证实CUL4B蛋白在结肠癌组织中表达高于配对癌旁组织。不同临床AJCC分期、肿瘤浸润深度、淋巴结转移、远处转移、血管浸润及组织学分型的结肠癌患者结肠癌组织中,CUL4B蛋白表达水平均不同(P<0.01)。结论 CUL4B蛋白在结肠癌中异常高表达,可能是新型结肠癌相关的靶标基因,其可能参与了结肠癌的进展过程。

Objective To validate the colon cancer related target gene CUL4B,and further to explore the expression pattern and invesgiate its relation with the pathological features. Methods Immunohistochemistry on a tissue microarray containing 203 cases of colon cancer was used to identify CUL4B expression patterns and analyze the relation between CUL4B expression and clinicopathological characteristics. Furthermore,western blotting was used to validate CUL4B expression in tumor tissue and the paired adjacent normal mucosa from patients with colon cancer. Results Immunohistochemistry studies on tissue microarray showed that CUL4B was mainly expressed in nucleus of colon cancer cells and the expression level was significantly higher in colon cancer tissues than that in the paired normal mucosa. Of the 203 normal mucosa specimens in the TMA,92.61%（188/203）showed negative CUL4B expression,6.40%（13/203）weak and 0.99%（2/203）specimens displayed strong staining. In contrast,the immunoreactive patterns of CUL4B were predominantly positively identified in the majority of colon cancer specimens. Overexpression of CUL4B was significantly correlated with American Joint Committee on cancer（AJCC）stage,depth of tumor invasion,lymph node metastasis,vascular invasion,histologic differentiation and distant metastasis（P〈0.01）. Furthermore,Western blotting analysis confirmed that CUL4B protein levels were significantly overexpressed in tumor tissue as compared with its paired normal mucosa,consistent with the results of immunohistochemistry. Conclusion We identified CUL4B as a new colon cancer related target gene. CUL4B was significantly overexpressed in colon cancer and probably play an important role in colon cancer carcinogenesis.