DNA聚合酶δ催化亚基基因在三阴性乳腺癌组织中的表达及其与预后的关系研究

DNA poly merase chain catalytic subunit gene expression in Triple-negative breast cancer

目的观察三阴性乳腺癌组织与对应癌旁组织中DNA聚合酶δ催化亚基基因(POLD1)的表达及其与预后的相关性。方法采用荧光定量PCR及免疫组织化学的方法检测110例三阴性乳腺癌患者癌组织标本及其对应的癌旁正常组织标本中POLD1蛋白的表达情况。分析POLD1蛋白的差异表达与患者临床病理特征及与预后的关系。结果110例癌组织中POLD1表达阳性81例(73.6%),阴性29例(26.4%)。癌旁组织中,POLD1表达阳性24例(21.8%),阴性86例(78.2%)。POLD1在癌组织中表达阳性率明显高于癌旁正常组织(χ^2=59.195,P<0.001)。POLD1的表达与组织学分级、TNM分期和淋巴结转移有关(P=0.002、0.010和0.018),与年龄、肿瘤大小、Ki-67标记指数、p53和表皮生长因子受体表达等无关。采用Kaplan-Meier法分析总生存期和无进展生存期,POLD1高表达组患者的无进展生存期明显短于POLD1低表达组(P=0.038),总生存期与POLD1低表达组比较差异无统计学意义(P>0.05)。Cox回归分析结果显示,POLD1表达、TNM分期、淋巴结转移是影响三阴性乳腺癌患者无进展生存期的独立危险因素(风险比=0.380,95%置信区间:0.147~0.985;风险比=4.816,95%置信区间:1.856~12.496;风险比=2.810,95%置信区间:1.435~5.506;均P<0.05)。结论POLD1蛋白的高表达提示三阴性乳腺癌较差的临床预后。

Objective To explore the expression of DNA polymeraseδcatalytic subunit gene(POLD1 in triple-negative breast cancer(TNBC).Methods The levels of POLD1 protein in 110 TNBC tissue specimens and the para-cancerous tissues were detected by immunohistochemistry.The relation among POLD1 protein,pathological features and prognosis of patients was analyzed.Results In 110 cancer tissues,81 cases(73.6%)were positive for POLD1 expression and 29 cases(26.4%)were negative.In adjacent tissues,24 cases(21.8%)were positive for POLD1 expression and 86 cases(78.2%)were negative.POLD1 expression was inconsistent in cancer tissues and adjacent tissues;it was significantly higher in cancer tissues than in adjacent tissues(χ^2=59.195,P<0.001).The expression of POLD1 was related to histological grade,TNM stage and lymph node metastasis(P=0.002,0.010,and 0.018);it was not related to age,tumor size,Ki-67 marker index,p53 and EGFR expression.The Kaplan-Meier method was used to analyze the overall survival and disease-free survival.The disease-free survival of patients with high expression of POLD1 was significantly shorter than that of patients with low expression of POLD1(P=0.038),but it had no significant effect on overall survival(P>0.05).In addition,Cox proportional hazards model showed that POLD1 expression,lymph node metastasis and TNM staging were independent risk factors of DFS(risk ratio=0.380,95%confidence interval:0.147-0.985;hazard ratio=4.816,95%confidence interval:1.856-12.496;hazard ratio=2.810,95%confidence interval:1.435-5.506;all P<0.05).Conclusion The high expression of POLD1 may be related with the poor clinical outcome of TNBC.