ZC3H13和m6a甲基转移酶WTAP在结肠癌中的表达水平及与预后的关系

Expression of ZC3H13 and m6a methyltransferase WTAP in colon cancer and their relationship with prognosis

目的探讨锌指含CCCH结构域蛋白13(ZC3H13)、N6-甲基腺苷(m6a)甲基转移酶肾母细胞瘤1相关蛋白(WTAP)在结肠癌患者组织中的表达情况及与患者预后的关系。方法选取2017年1月-2019年6月在芜湖市中医医院手术治疗的结肠癌患者80例为研究对象,并在术中收集患者癌组织标本及癌旁组织标本,采用免疫组织化学染色法观察结肠癌组织中ZC3H13、WTAP表达情况,Western blot法检测组织中ZC3H13、WTAP表达水平;收集患者临床病理参数并对患者进行3年随访,Pearson法分析ZC3H13与WTAP表达的相关性;利用Kaplan-Meier法绘制生存曲线;采用多因素Cox回归风险模型分析结肠癌患者的预后影响因素。结果结肠癌患者癌组织WTAP表达水平高于癌旁组织[(1.66±0.23)vs.(0.58±0.17)],ZC3H13表达水平低于癌旁组织[(0.45±0.09)vs.(1.04±0.22)],差异均有统计学意义(t=33.775、22.201,P均<0.05);结肠癌组织中ZC3H13和WTAP的表达水平成负相关(r=-0.615,P<0.05);结肠癌组织中ZC3H13、WTAP蛋白表达与远处转移、临床分期、分化程度、浸润深度有关(P<0.05);Kaplan-Meier分析结果显示,WTAP阳性表达患者3年累积生存率48.33%(29/60)显著低于阴性表达80.00%(16/20),差异有统计学意义(Log rankχ^(2)=6.219,P=0.013);ZC3H13阳性表达患者3年累积生存率83.33%(15/18)显著高于阴性表达患者48.39%(30/62),差异有统计学意义(Log rankχ^(2)=6.697,P=0.010);多因素Cox回归分析结果显示WTAP阳性、ZC3H13阴性、年龄(>60岁)、淋巴结转移(N2)、远处转移、临床分期(Ⅲ+Ⅳ)、浸润深度(T3+T4)均是影响患者预后的危险因素(P<0.05)。结论ZC3H13在结肠癌患者癌组织中表达降低,WTAP表达升高,二者表达水平与结肠癌患者临床特征及预后关系密切。

Objective To investigate the expression of zinc finger CCCH domain-containing protein 13(ZC3H13)and N6-methyladenosine(m6a)methyltransferase Wilms tumor 1 associated protein(WTAP)in the tissues of patients with coloncancer and their relationship with the prognosis of patients.MethodsFrom January 2017 to June 2019,80 patients withcolon cancer who were surgically treated in our hospital were gathered as the research objects,and 80 cancer tissuespecimens and paracancerous tissue specimens were collected from patients during the operation.Immunohistochemicalstaining was used to observe the expression of ZC3H13 and WTAP in colon cancer tissue;Western blot was used to detectthe expression levels of ZC3H13 and WTAP in tissues;the clinicopathological parameters of the patients were collected andthe patients were followed up for 3 years.The correlation between ZC3H13 and WTAP expression was analyzed by Pearsonmethod;Kaplan-Meier method was used to draw survival curves;multivariate Cox regression risk model was used to analyzethe prognostic factors of colon cancer patients.ResultsThe expression level of WTAP in cancer tissue of colon cancerpatients was higher than that in adjacent tissue[(1.66±0.23)vs.(0.58±0.17)],and the expression level of ZC3H13 waslower than that in adjacent tissue[(0.45±0.09)vs.(1.04±0.22)],the differences were statistically significant(t=33.775,22.201,P<0.05);the expression levels of ZC3H13 and WTAP in colon cancer tissues were obviously negatively correlated(r=-0.615,P<0.05);the expression of ZC3H13 and WTAP proteins in colon cancer tissue was related to distant metastasis,clinical stage,degree of differentiation and depth of invasion(P<0.05);Kaplan-Meier analysis showed that the 3-yearcumulative survival rate of patients with positive WTAP expression was 48.33%(29/60),which was obviously lower thanthat of patients with negative expression,80.00%(16/20)(Log rankχ^(2)=6.219,P=0.013);the 3-year cumulative survivalrate of patients with positive ZC3H13 expression was 83.33%(15/18),which was obviously higher than that of patients withnegative ZC3H13 expression,48.39%(30/62)(Log rankχ^(2)=6.697,P=0.010);the results of multivariate Cox regressionanalysis showed that positive WTAP,negative ZC3H13,age>60 years old,lymph node metastasis(N2),distant metastasis,clinical stage(Ⅲ+Ⅳ),and depth of invasion(T3+T4)were all risk factors affecting the prognosis of patients(P<0.05).ConclusionThe expression of ZC3H13 was decreased in the cancer tissue of colon cancer patients,and the expression ofWTAP was increased,and the expressions of the two were closely related to the clinical characteristics and prognosis of coloncancer patients.