结直肠癌组织中卷曲螺旋结构域12蛋白表达与肿瘤生长侵袭的关系

Effect of Coiled-coil domain-containing protein 12 on growth and invasion of colorectal cancer tissues

摘要:

目的观察结直肠癌组织中卷曲螺旋结构域12（CCDC12）蛋白的表达情况，并探讨CCDC12蛋白与肿瘤生长侵袭的关系。方法免疫组织化学SP法检测94 例结直肠癌组织及癌旁正常肠黏膜组织中CCDC12蛋白的表达，同时检测与肿瘤生长侵袭有关的蛋白质Cyclin D1、P21、MMP-9 及TIMP-1 蛋白表达。记录患者肿瘤生物学特征，分析CCDC12 蛋白与结直肠癌生物学特征及Cyclin D1、P21、MMP-9及TIMP-1蛋白的关系。结果CCDC12、CyclinD1、MMP-9 及TIMP-1 蛋白在结直肠癌组织中阳性表达率均高于癌旁正常肠黏膜组织（χ2=38.480、30.312、38.368 及7.667，均P<0.01），P21 蛋白在两种组织中差异无统计学意义（χ2=0.862，P =0.353）。在结直肠癌组织中CCDC12 蛋白阳性表达与肿瘤细胞分化、浸润深度、淋巴结转移及TNM 分期有关（χ2=5.130、5.902、9.760 及4.458，P =0.024、0.015、0.002 及0.035）。Spearman 相关性分析发现，CCDC12 与Cyclin D1、MMP-9蛋白表达呈正相关（r =0.302和0.365，p =0.003和0.001），CCDC12与P21表达呈负相关（r =-0.287，p =0.005）。结论结直肠癌中存在CCDC12 蛋白表达增高现象，CCDC12 可能通过与CyclinD1、P21及MMP-9 蛋白的相互作用参与了结直肠癌的生长及侵袭过程。

Abstract:

Objective To investigate the effect of Coiled-coil domain-containing protein 12 (CCDC12) on growth and invasion of colorectal cancer. Methods Immunohistochemistry (IHC) was used to detect expression of CCDC12 in 94 cases of colorectal cancer and associated adjacent healthy tissues. Growth and invasion related proteins including CyclinD1, P21, matrix metallopeptidase 9 (MMP -9), tissue inhibitor of metalloproteinase 1 (TIMP-1) were also determined. Biological characteristics of cancer were recorded and correlated with concentrations of CCDC12, CyclinD1, P21, MMP -9, TIMP -1 proteins. Results Positive expression rates of CCDC12, CyclinD1, MMP-9 and TIMP-1 in colorectal cancer tissues were significantly increased when compared with those in healthy tissues (x2 = 38.480, 30.312, 38.368 and 7.667, respectively)(P < 0.01) while no significant difference was observed in concentration of P21 in the tissues (x2= 0.862,p =0.353). Intimate correlations of CCDC12 with characters of tumor such as differentiation, depth of invasion,lymphatic metastasis, and TNM stages (x2 = 5.130, 5.902, 9.760 and 4.458; p= 0.024, 0.015, 0.002 and 0.035,respectively) were observed. Spearman correlation analysis showed that the expression of CCDC12 was positively correlated with Cyclin D1 and MMP-9 (x2 = 0.302 and 0.365, p= 0.003 and 0.001, respectively) while negative correlation was found between CCDC12 and P21 (x2 = -0.287,p = 0.005). Conclusions CCDC12 is highly expressed in colorectal cancer, which affects Cyclin D1-, P21- and MMP-9-mediated growth and metastasis of colorectal cancer.