TRAF6和OTUD5在结直肠癌中的表达情况及其临床意义

Expressions of TRAF6 and OTUD5 in colorectal canceRand theiRclinical significances

目的探讨肿瘤坏死因子受体相关因子6(TRAF6)和卵巢肿瘤结构域蛋白去泛素化酶5(OTUD5)在结直肠癌(CRC)中的表达情况及其在CRC发生、发展中的机制作用。方法收集2017年3月至2018年3月在广西医科大学第一附属医院接受手术治疗的50例CRC患者的临床病理资料。选取患者肿瘤的CRC组织及其对应的癌旁组织(距离肿瘤边缘>10 cm),采用免疫组织化学染色法检测TRAF6和OTUD5的表达情况,并分析其与患者临床病理特征的关联性。采用实时荧光定量聚合酶链式反应(RT-qPCR)法检测TRAF6 mRNA和OTUD5 mRNA在人正常结肠上皮细胞株NCM460和CRC细胞株HT29的表达水平。构建过表达TRAF6的HT29细胞系,分析TRAF6与OTUD5的相关性。结果CRC组织的TRAF6阳性表达率显著高于癌旁组织(84.00%vs 28.00%;χ^(2)=31.818,P=0.000),OTUD5阳性表达率显著低于癌旁组织(32.00%vs 54.00%;χ^(2)=4.937,P=0.026)。TRAF6阴性组远处转移发生率显著高于TRAF6阳性组(P<0.05)。OTUD5阴性组TNM分期为Ⅲ~Ⅳ期的人数比例大于OTUD5阳性组,且淋巴结转移和远处转移发生率高于OTUD5阳性组,差异有统计学意义(P<0.05)。HT29细胞的TRAF6 mRNA表达水平显著高于NCM460细胞(t=6.960,P=0.000),OTUD5 mRNA表达水平显著低于NCM460细胞(t=13.840,P=0.000)。过表达TRAF6的HT29细胞的OTUD5 mRNA表达水平显著低于正常HT29细胞(t=32.555,P=0.000)。结论TRAF6可能通过抑制OTUD5基因的表达调控CRC的发生、发展和转移。

Objective To explore the expressions of tumoRnecrosis factoRreceptor-associated factoR6(TRAF6)and deubiquitinating enzyme ovarian tumoRdomain-containing protein 5(OTUD5)in colorectal cancer(CRC),and theiRroles in the development and progression of colorectal cancer.Methods The clinicopathological data of 50 CRC patients who underwent surgical treatment in the First Affiliated Hospital of Guangxi Medical University from March 2017 to March 2018 were selected.The CRC tissues and theiRmatched paracancerous tissues(>10 cm from the tumoRedge)were collected,and the expressions of TRAF6 and OTUD5 were detected by immunohistochemical staining,and theiRcorrelations with the clinicopathological characteristics of the patients were analyzed.The expression levels of TRAF6 mRNA and OTUD5 mRNA in human normal colon epithelial cell line NCM460 and CRC cell line HT29 were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)method.The HT29 cell line overexpressing TRAF6 was constructed,and the correlation between TRAF6 and OTUD5 was analyzed.Results The positive expression rate of TRAF6 in the CRC tissues was significantly higheRthan that in the matched paracancerous tissues(84.00%vs 28.00%;χ^(2)=31.818,P=0.000),and the positive expression rate of OTUD5 in the CRC tissues was significantly loweRthan that in the matched paracancerous tissues(32.00%vs 54.00%;χ^(2)=4.937,P=0.026).The incidence of distant metastasis in the TRAF6-negative group was significantly higheRthan that in the TRAF6-positive group(P<0.05).The OTUD5-negative group had a greateRproportion of the patients with TNM stageⅢ~Ⅳthan the OTUD5-positive group,and the incidence rates of lymph node metastasis and distant metastasis in the OTUD5-negative group were higheRthan those in the OTUD5-positive group,and the differences were statistically significant(P<0.05).The expression level of TRAF6 mRNA in HT29 cells was significantly higheRthan that in NCM460 cells(t=6.960,P=0.000),and the expression level of OTUD5 mRNA in HT29 cells was significantly loweRthan that in NCM460 cells(t=13.840,P=0.000).In the HT29 cells overexpressing TRAF6,the expression level of OTUD5 mRNA was significantly loweRthan that in the normal HT29 cells(t=32.555,P=0.000).Conclusion TRAF6 may be involved in the occurrence,development and metastasis of CRC by inhibiting the expression of OTUD5 gene.