[关键词]
[摘要]
目的:探讨转录因子粒状头样2(GRHL2)在乳腺癌组织中的表达及其与患者临床病理特征和预后的关系,为乳腺的临床治疗寻找新的靶点。方法:选取2010 年1 月至2017 年1 月在新乡市中心医院普外二科诊疗并经病理确认的初发乳腺癌患者88 例的癌组织及相应的癌旁组织。免疫组织化学染色法检测GRHL2 在乳腺癌组织及相应的癌旁组织中的表达,并分析GRHL2 的表达水平与患者临床病理特征的关系;通过分析TCGA乳腺癌临床数据,探究GRHL2 的表达与乳腺癌患者预后的关系。结果:乳腺癌组织中GRHL2 的表达率(75.00%)明显高于癌旁组织(36.36%)(P<0.01)。TCGA数据库中114 例正常乳腺组织以及1 097 例原发性乳腺癌组织中GRHL2 的表达结果显示,原发性乳腺癌组织中GRHL2 的表达高于正常乳腺组织,差异有统计学意义(P<0.01)。GRHL2 的表达与乳腺癌TNM分期、组织学分级、HER2 表达、淋巴结转移状态等相关(均P<0.05);通过分析TCGA数据库中1 979 例低表达GRHL2 乳腺癌患者与1 972 例高表达GRHL2 乳腺癌患者无复发生存期(RFS)结果显示,高表达GRHL2 的乳腺癌患者RFS患者显著缩短(HR=1.24,95%CI:1.11~1.38,P<0.01);GRHL2表达差异对TNBC乳腺癌患者的RFS无明显影响(HR=1.30,95%CI: 0.89~1.88,P=0.170);GRHL2 的表达差异对ER+乳腺癌患者的RFS 无明显影响(HR=1.17,95%CI:0.76~1.78,P=0.470);但是高表达GRHL2 的HER2+乳腺癌患者其RFS显著低于低表达GRHL2 的HER2+乳腺癌患者(HR=1.72,95%CI:1.11~2.68,P=0.015)。结论:GRHL2 在乳腺癌组织中表达升高,并与HER2 表达、组织学分级、TNM分期、淋巴结转移密切相关,在乳腺癌发生发展过程中发挥重要作用,提示不良预后。
[Key word]
[Abstract]
Objective: To detect the expression of GRHL2 (grainyhead-like-2) in breast cancer tissues and to explore its correlation with clinicopathological characteristics and prognosis of breast cancer (BC) patients,aiming to find new therapeutic target for breast cancer. Method: A total of 88 pairs of BC tissues and corresponding para-cancerous tissues from patients with primary BC that treated and pathologically confirmed at the Second Department of General Surgery, Xinxiang Central Hospital from January 2010 to January 2017 were collected for this study. The expression of GRHL2 in BC tissues and para-cancerous tissues was examined with IHC, and the association between GRHL2 and clinicopathological characteristics of BC patients was analyzed. Moreover, the correlation between GRHL2 and prognosis of BC patients was investigated by analyzing TCGA clinic data for BC. Result: The expression of GRHL2 was significantly higher in BC tissues (75.00%) compared with para-cancerous tissues (36.36%) (P<0.01); Based on the results of GRHL2 expression in 114 cases of normal breast tissues and 1 097 cases of primary breast cancer tissues in TCGA database, the expression of GRHL2 in primary BC tissues was significantly higher than that in normal breast tissues (P<0.01). GRHL2 expression was associated with BC TNM stage, histological grade, HER2 status and lymphnode metastasis status (all P<0.05); TCGA database showed that the RFS of 1 979 BC patients with high GRHL2 expression was significantly shorter than that of the 1 972 cases of BC patients with low GRHL2 expression (HR=1.24, 95%CI:1.11-1.38, P<0.01); GRHL2 expression exerted no significant effect on RFS of TNBC patients or ER+ BC patients (TNBC: HR=1.30,95%CI: 0.89-1.88,P=0.170; ER+ : HR=1.17, 95%CI: 0.76-1.78,P=0.470); however, the RFS of HER2+ BC patients with high GRHL2 expression was significantly shorter than that of HER2+ BC patients with low GRHL2 expression (HR=1.72, 95%CI:1.11-2.68, P=0.015). Conclusion:Expression level of GRHL2 was up-regulated in BC tissues, and was associated with BC TNM stage, histological grade, HER2 status and the lymphnode metastasis status. GRHL2 plays an important role in the generation and development of BC, indicating poor prognosis.
[中图分类号]
[基金项目]