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

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、Cyclin D1、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(χ~2=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(χ~2=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(χ~2=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Cyclin D1、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。

Objective To investigate the effect of Coiled-coil domain-containing protein 12 （CCDC12） ongrowth and invasion of colorectal cancer. Methods Immunohistochemistry （IHC） was used to detect expressionof CCDC12 in 94 cases of colorectal cancer and associated adjacent healthy tissues. Growth and invasionrelated proteins including CyclinD1, P21, matrix metallopeptidase 9 （MMP -9）, tissue inhibitor ofmetalloproteinase1 （TIMP -1） were also determined. Biological characteristics of cancer were recorded andcorrelated with concentrations of CCDC12, CyclinD1, P21, MMP -9, TIMP -1 proteins. Results Positiveexpression rates of CCDC12, CyclinD1, MMP-9 and TIMP-1 in colorectal cancer tissues were significantlyincreased when compared with those in healthy tissues （x2= 38.480, 30.312, 38.368 and 7.667, respectively）（ 〈 0.01） while no significant difference was observed in concentration of P21 in the tissues （x2= 0.862, =0.353）. Intimate correlations of CCDC12 with characters of tumor such as differentiation, depth of invasion,lymphatic metastasis, and TNM stages（字2= 5.130, 5.902, 9.760 and 4.458; = 0.024, 0.015, 0.002 and 0.035,respectively） were observed. Spearman correlation analysis showed that the expression of CCDC12 waspositively correlated with Cyclin D1 and MMP-9 （ = 0.302 and 0.365, = 0.003 and 0.001, respectively）while negative correlation was found between CCDC12 and P21 （ = -0.287, = 0.005）. Conclusions CCDC12is highly expressed in colorectal cancer, which affects Cyclin D1-, P21- and MMP-9-mediated growth andmetastasis of colorectal cancer.