DUOXA2在结直肠癌组织中表达及其与预后的关联

Expression of DUOXA2 in colorectal cancer and its relationship with prognosis

目的探讨双氧化酶成熟因子2(DUOXA2)在结直肠癌组织中的表达及其与患者预后的关系。方法选取河北医科大学第四医院2018-10-01-2019-07-01接受手术治疗的结直肠癌患者75例的肠癌组织和配对癌旁正常组织,qRT-PCR法检测DUOXA2在结直肠癌组织与配对癌旁正常组织中的mRNA表达水平,分析其在肠癌组织与癌旁正常组织中的表达差异,以及其在结直肠癌组织中的表达与临床病理学因素之间的关联性。收集2011-09-01-2016-09-01河北医科大学第四医院晚期转移性结直肠癌患者50例的蜡块标本,所有患者均取其癌旁正常组织、结直肠癌组织、转移淋巴结组织以及肝脏转移瘤组织的蜡块标本,免疫组化法检测DUOXA2蛋白在以上4种不同组织中的表达情况,采用χ^(2)检验分析不同组织中DUOXA2蛋白的表达差异。采用Cox单因素及多因素分析。结果结直肠癌组织中DUOXA2的mRNA的表达(0.1515±0.2565)明显高于癌旁正常组织(0.0774±0.2046),Z=0.597,P<0.001。结直肠癌组织中DUOXA2的mRNA高表达比例:最大径>4 cm(69.4%)高于最大径≤4 cm(33.3%),差异有统计学意义,χ^(2)=9.766,P=0.002;淋巴结转移阳性(65.5%)高于淋巴结转移阴性(41.3%),差异有统计学意义,χ^(2)=4.172,P=0.041。DUOXA2蛋白在晚期转移性结直肠癌患者不同组织中的表达差异有统计学意义,χ^(2)=89.376,P<0.001。单因素Cox分析显示,DUOXA2蛋白高表达(HR=3.927,P<0.001,95%CI为2.175~7.090)、ECOG评分1~2分(HR=2.207,P=0.006,95%CI为1.260~3.868)和低分化(HR=2.229,P=0.010,95%CI为1.214~4.095)是预测晚期转移性结直肠癌患者生存的预后的危险性因素。多因素Cox分析显示,DUOXA2蛋白高表达(HR=3.638,P<0.001,95%CI为1.943~6.811)、ECOG评分1~2分(HR=1.836,P=0.047,95%CI为1.008~3.342)和组织低分化(HR=3.958,P=0.004,95%CI为1.555~10.073)是预测晚期转移性结直肠癌患者生存的独立预后的危险性因素,P<0.05。结论DUOXA2在结直肠癌组织中高表达,且与肿瘤最大径、淋巴结转移相关。转移组织中DUOXA2蛋白表达显著高于原发肠癌组织,且肠癌组织中DUOXA2蛋白高表达与晚期转移性结直肠癌患者的不良预后密切相关,可能是结直肠癌患者潜在的生物标记物。

Objective To explore the expression of DUOXA2 in colorectal cancer(CRC)and its relationship with prognosis.Methods The expression of DUOXA2 mRNA was analyzed in 75 pairs of CRC tissues and the paired normal tissues from October 1,2018 to July 1,2019 at the Fourth Hospital of Hebei Medical University by qRT-PCR.The correlation between DUOXA2 mRNA and clinicopathological factors was also analyzed.Paraffin specimens of 50 patients with metastatic colorectal cancer were collected from September 1,2011 to September 1,2016,including normal tissues,cancer tissues,metastatic lymph node tissues and metastatic liver tissues.The expression of DUOXA2 protein was analyzed by Immunohistochemistry.The relationship between DUOXA2 protein and survival time was also analyzed.Cox regression was used to predict the risk of clinical-pathological parameters.Results The expression of DUOXA2 mRNA in CRC tissues(0.1515±0.2565)was significantly higher than that in the paired normal tissues(0.0774±0.2046)(Z=0.597,P<0.001).The proportion of DUOXA2 overexpression in tumor tissues with maximum diameter>4 cm(69.4%)was significantly higher than that in tumor tissues with tumor diameter≤4 cm(33.3%)(χ^(2)=9.766,P=0.002).The proportion of DUOXA2 overexpression in tumor tissues with positive lymph node metastasis(65.5%)was significantly higher than that in tumor tissues with negative lymph node metastasis(41.3%)(χ^(2)=4.172,P=0.041).There were significant differences in the expression of DUOX2 protein in different tissues of metastatic colorectal cancer patients(χ^(2)=89.376,P<0.001).Univariate Cox regression analysis showed that high expression of DUOXA2 protein(HR=3.927,P<0.001,95%CI:2.175-7.090),ECOG score 1-2(HR=2.207,P=0.006,95%CI:1.260-3.868),low differentiation(HR=2.229,P=0.010,95%CI:1.214-4.095)were risk factors for survival and prognosis of metastatic colorectal cancer patients.Multivariate Cox regression analysis showed that high expression of DUOXA2 protein(HR=3.638,P<0.001,95%CI:1.943-6.811),ECOG score 1-2(HR=1.836,P=0.047,95%CI:1.008-3.342)and low differentiation(HR=3.958,P=0.004,95%CI:1.555-10.073)were independent factors of death in metastatic colorectal cancer patients(P<0.05).Conclusions DUOXA2 was highly expressed in CRC tissues and was associated with the tumor diameter and lymph node metastasis.The expression of DUOXA2 protein in metastatic tissues was significantly higher than that in CRC tissues and the high expression of DUOXA2 protein in CRC tissues was closely related with poor prognosis,which indicated that DUOXA2 may be a potential biomarker for CRC patients.