2020 年第 8 期 第 15 卷

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

作者：夏地也·吐尔洪1甫拉提·吾瓦力汉1依日夏提·艾海提2张明帅1蒋威华1

英文作者：Xiadiye Tuerhong1 Fulati Wuwalihan1 Yirixiati Aihaiti2 Zhang Mingshuai1 Jiang Weihua1

单位：1新疆医科大学附属肿瘤医院乳腺外科，乌鲁木齐830011；2西安交通大学2017级硕士研究生710000 

英文单位：1Department of Breast Surgery Tumor Hospital Affiliated to Xinjiang Medical University Urumqi 830011 China； 2 2017 Graduate Student of Xi′an Jiaotong University Xi′an 710000  China

关键词：三阴性乳腺癌；DNA聚合酶δ催化亚基基因

英文关键词：riple-negativebreastcancer;DNApolymerasechaincatalyticsubunitgene

• 摘要：

• 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(χ2=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 polymerase δ catalytic 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 (χ2=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.