脯氨酸、谷氨酸、亮氨酸丰富蛋白1（PELP1）在三阴性乳腺癌中的预后意义：一项对129例病例的回顾性研究
Prognostic significance of proline, glutamic acid, leucine rich protein 1 (PELP1) in triple-negative breast cancer: a retrospective study on 129 cases.
作者信息
Zhang Yanzhi, Dai Jiali, McNamara Keely M, Bai Bing, Shi Mumu, Chan Monica S M, Liu Ming, Sasano Hironobu, Wang Xiuli, Li Xiaolei, Liu Lijuan, Ma Ying, Cao Shuwen, Xing Yanchun, Zhao Baoshan, Song Yinli, Wang Lin
机构信息
Department of Pathology, Harbin Medical University-Daqing, No. 39 Xinyang Road, Hi-Tech Zone, Daqing, Heilongjiang, China.
Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
出版信息
BMC Cancer. 2015 Oct 15;15:699. doi: 10.1186/s12885-015-1694-y.
BACKGROUND
Triple-negative breast cancer (TNBC) is associated with an aggressive clinical course due to the lack of therapeutic targets. Therefore, identifying reliable prognostic biomarkers and novel therapeutic targets for patients with TNBC is required. Proline, glutamic acid, leucine rich protein 1 (PELP1) is a novel steroidal receptor co-regulator, functioning as an oncogene and its expression is maintained in estrogen receptor (ER) negative breast cancers. PELP1 has been proposed as a prognostic biomarker in hormone-related cancers, including luminal-type breast cancers, but its significance in TNBC has not been studied.
METHODS
PELP1 immunoreactivity was evaluated using immunohistochemistry in 129 patients with TNBC. Results were correlated with clinicopathological variables including patient's age, tumor size, lymph node stage, tumor grade, clinical stage, histological type, Ki-67 LI, as well as clinical outcome of the patients, including disease-free survival (DFS) and overall survival (OS).
RESULTS
PELP1 was localized predominantly in the nuclei of carcinoma cells in TNBC. With the exception of a positive correlation between PELP1 protein expression and lymph node stage (p = 0.027), no significant associations between PELP1 protein expression and other clinicopathological variables, including DFS and OS, were found. However, when PELP1 and Ki-67 LI were grouped together, we found that patients in the PELP1/Ki-67 double high group (n = 48) demonstrated significantly reduced DFS (p = 0.005, log rank test) and OS (p = 0.002, log rank test) than others (n = 81). Multivariable analysis supported PELP1/Ki-67 double high expression as an independent prognostic factor in patients with TNBC, with an adjusted hazard ratio of 2.020 for recurrence (95 % CL, 1.022-3.990; p = 0.043) and of 2.380 for death (95 % CL, 1.138-4.978; p = 0.021).
CONCLUSIONS
We found that evaluating both PELP1 and Ki-67 expression in TNBC could enhance the prognostic sensitivity of the two biomarkers. Therefore, we propose that PELP1/Ki-67 double high expression in tumors is an independent prognostic factor for predicting a poor outcome for patients with TNBC.
背景
三阴性乳腺癌（TNBC）因缺乏治疗靶点而具有侵袭性临床病程。因此，需要为TNBC患者确定可靠的预后生物标志物和新的治疗靶点。脯氨酸、谷氨酸、亮氨酸丰富蛋白1（PELP1）是一种新型甾体受体共调节因子，作为一种癌基因发挥作用，其表达在雌激素受体（ER）阴性乳腺癌中得以维持。PELP1已被提议作为激素相关癌症（包括管腔型乳腺癌）的预后生物标志物，但其在TNBC中的意义尚未得到研究。
方法
采用免疫组织化学法评估129例TNBC患者的PELP1免疫反应性。结果与临床病理变量相关，包括患者年龄、肿瘤大小、淋巴结分期、肿瘤分级、临床分期、组织学类型、Ki-67标记指数，以及患者的临床结局，包括无病生存期（DFS）和总生存期（OS）。
结果
PELP1主要定位于TNBC癌细胞的细胞核中。除PELP1蛋白表达与淋巴结分期呈正相关（p = 0.027）外，未发现PELP1蛋白表达与其他临床病理变量（包括DFS和OS）之间存在显著关联。然而，当将PELP1和Ki-67标记指数分组时，我们发现PELP1/Ki-67双高组（n = 48）的患者与其他患者（n = 81）相比，DFS（p = 0.005，对数秩检验）和OS（p = 0.002，对数秩检验）显著降低。多变量分析支持PELP1/Ki-67双高表达是TNBC患者的独立预后因素，复发的调整风险比为2.020（95%置信区间，1.022 - 3.990；p = 0.043），死亡的调整风险比为2.380（95%置信区间，1.138 - 4.978；p = 0.021）。
结论
我们发现评估TNBC中PELP1和Ki-67的表达可以提高这两种生物标志物的预后敏感性。因此，我们提出肿瘤中PELP1/Ki-67双高表达是预测TNBC患者不良结局的独立预后因素。
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