Krüppel样转录因子12在结直肠癌患者肿瘤组织和血清中的表达及其意义

目的：检测Krüppel样转录因子12（KLF12）蛋白在结直肠癌患者肿瘤组织和血清中的表达，并探讨其临床价值。方法：选择120例结直肠癌手术患者作为研究对象（病例组），收集结直肠癌组织和癌旁组织的石蜡标本，选择体检正常者100人作为对照组。免疫组织化学染色检测结直肠癌组织和癌旁肠组织中KLF12、nm23、周期素E1（CyclinE1）、基质金属蛋白酶2（MMP-2）和MMP-9蛋白的表达情况；ELISA法检测手术前和术后1个月时患者血清中KLF12水平并检测对照组受试者血清中KLF12水平。结果：结直肠癌组织中KLF12、CyclinE1、MMP-2和MMP-9蛋白阳性表达率高于癌旁组织（χ²=66.155，52.795，64.515，52.632；P<0.001），nm23蛋白阳性表达率低于癌旁组织（χ²=13.019，P<0.001）。Spearman相关分析，结直肠癌组织中KLF12蛋白与MMP-2和MMP-9蛋白表达水平呈正相关关系（r=0.396 3，P<0.001；r=0.326 4，P<0.001），与nm23蛋白表达水平呈负相关关系（r=-0.227 3，P=0.013）。病例组结直肠癌患者手术前血清中KLF12蛋白表达水平高于对照组，血清中KLF12蛋白表达水平受试者工作特征曲线（ROC）的最佳cut-off值为3.795 μg·L^-1，曲线下面积为0.834，其对诊断结直肠癌的敏感度和特异度分别为60.8%和94.0%。病例组结直肠癌患者手术后血清中KLF12蛋白表达水平降低，但仍高于对照组（t=2.708，P=0.007）；结直肠癌组织中KLF12蛋白表达水平与血清中KLF12蛋白表达水平呈正相关关系（r=0.406 9，P<0.001）。淋巴结转移程度为N3的（N3组）患者血清中KLF12水平最高，N0组患者最低（F=21.731，P<0.001）。结论：KLF12蛋白可能参与了结直肠癌的侵袭转移，检测患者血清中KLF12蛋白表达水平可能对判断病情和预测淋巴结转移有价值。

Expressions of Krüppel-like factor 12 in cancer tissue and serum of patients with colorectal cancer and their significances

Objective:To detect the expressions of Krüppel-like factor 12 (KLF12)protein in the cancer tissue and serum of the patients with colorectal cancer,and to investigate their clinical values.Methods:A total of 120 colorectal cancer patients were selected as case group,and 100 normal cases were regarded as control group. The cancer tissue and adjacent mucosa tissue were collected.Immunohistochemical method was used to detect the expressions of KLF12,nm23,CyclinE1,matrix metalloproteinase-2 (MMP-2),and MMP-9 proteins,and the relationships among these proteins were evaluated.ELISA assay was applied to detect the serum KLF12 levels of the patients in case group before operation and 1 month after operation the levels of serum KLF12 of the subjects in control group.Results:The positive expression rates of KLF12,CyclinE1,MMP-2 and MMP-9 proteins in cancer tissue were higher than those in adjacent mucosa tissue (χ2 =66.155,52.795,64.515,52.632;P <0.001),while the positive expression rate of nm23 protein in cancer tissue was lower than that in adjacent mucosa tissue (χ2 =13.019,P <0.001).The Spearman analysis results showed that the expression of KLF12 protein was positively correlated with the expressions of MMP-2 and MMP-9 proteins (r=0.3963,P <0.001;r=0.3264,P <0.001);the expression of KLF12 was negatively correlated with the expression of nm23 protein (r = - 0.2273,P =0.013).The level of serum KLF12 of the patients in case group before operation was higher than that in control group.The cut-off value of ROC curve of serum KLF12 protein expression level was 3.795 μg·L-1 ,and the area under the ROC curve was 0.834.The sensitivity and specificity were 60.8% and 94.0%,respectively. After operation,the serum level of KLF12 protein in the patients in case group was decreased,which was still higher than that in control group (t=2.708,P =0.007).The expression level of KLF12 protein in cancer tissue was positively correlated with the level of serum KLF12 protein (r =0.4069,P <0.001).According to degree of lymph node metastasis,and the serum level of KLF12 protein in N3 group was the highest,and the lowest serum level of KLF12 protein was found in N0 group (F =21.731,P <0.001).Conclusion:KLF12 protein might be involved in the invasion and metastasis of colorectal cancer,and the detection of serum level of KLF12 protein could be valuable for the judgement of disease and prediction of lymph node metastasis of the patients.