结直肠癌中ARMCX2的表达及其临床意义

Expression of ARMCX2 in colorectal cancer and its clinical significance

目的探讨结直肠癌组织中ARM重复X连锁蛋白2(ARMCX2)的表达与临床病理特征的关系及与K-ras基因突变的相关性。方法选取2012年1月至2014年8月在浙江中医药大学附属第二医院确诊为结直肠癌的患者87例,并留取距结直肠癌组织边缘>3 cm的正常结肠黏膜组织(癌旁组织)87例作为对照。采用免疫组化法检测结直肠癌组织和癌旁组织中ARMCX2表达和结直肠癌中增殖细胞核抗原(PCNA)表达,Western blot检测结直肠癌组织中B细胞淋巴瘤/白血病-2(Bcl-2)和Bcl-2相关X蛋白(Bax)表达,qRT-PCR检测结直肠癌组织中K-ras基因突变并分析其与ARMCX2的相关性。结果结直肠癌组织中ARMCX2阳性表达率为51.7%,高于癌旁组织的10.3%,差异有统计学意义(P<0.01)。结直肠癌组织中PCNA阳性表达率为43.7%。结直肠癌组织中ARMCX2阳性表达与肿瘤最大径、浸润深度、淋巴结转移、血管淋巴管侵犯和TNM分期均有关(均P<0.05),而与性别、年龄和分化程度均无关(均P>0.05)。与癌旁组织相比,结直肠癌组织中Bax蛋白表达水平降低,Bcl-2蛋白表达水平升高,差异均有统计学意义(均P<0.05)。Pearson相关分析显示ARMCX2与BAX的表达呈负相关(r=0.63,P<0.01),与Bcl-2、PCNA的表达均呈正相关(r=0.35和0.70,均P<0.05)。有K-ras基因突变的结直肠癌组织中ARMCX2阳性表达率为85.7%,高于无K-ras基因突变的40.9%,差异有统计学意义(P<0.01)。结直肠癌患者术后生存时间为10~60个月,中位生存时间29个月。生存分析显示ARMCX2的表达与生存时间有关(P<0.05)。结论结直肠癌中ARMCX2表达升高,其高表达在促进肿瘤细胞增殖和凋亡过程中有重要作用。ARMCX2与K-ras基因突变有关。ARMCX2可能是结直肠癌重要的预后因子。

Objective To investigate the expression of ARM proteins lost in epithelial cancers X chromosome 2(ARMCX2)and Kirsten rat sarcoma viral oncogene(K-ras)gene mutation in colorectal cancer and its relationship with cli-nicopathological features.Methods The expressions of ARMCX2 and PCNA were detected by immunohistochemical method in colorectal cancer and corresponding pericancerous tissues of 87 patients with colorectal cancer.BAX and Bcl-2 were detected by Western blot.K-ras gene mutation was detected by real-time fluorescence quantitative PCR.Results There were significant differences in ARMCX2 expression between cancer tissues and pericancerous tissues(51.7%vs 10.3%,P<0.01).The positive expression rate of PCNA in colorectal cancer was 43.7%.Expression of ARMCX2 was significantly associated with tumor size,depth of invasion,lymph node metastasis,vascular and lymphatic vessel involvement and TNM staging in colorectal cancer(all P<0.05).Expression of ARMCX2 was not associated with patients'gender,age and degree of differentiation(all P>0.05).ARMCX2 was positively correlated with PCNA and Bcl-2(r=0.70 and 0.35,both P<0.05),and negatively correlated with BAX(r=0.63,P<0.01)in colorectal cancer.The expression rate of ARMCX2 in cancer tissues with K-ras gene mutation was higher than that without K-ras mutation(85.7%vs 40.9%,P<0.01).ARMCX2 was correlated with survival time(P<0.05).Conclusion The expression of ARMCX2 is upregulated in colorectal cancer,which is correlated with clinicopathological characteristics of patients.ARMCX2 is associated with K-ras gene mutation,indicating that high expression of ARMCX2 may play an important role in promoting the proliferation and inhibiting apoptosis of cancer cells.