【原】中国学者发现真核翻译起始因子可预测三阴性乳腺癌患者的无病生存

　　磷酸化真核翻译起始因子2α（p-eIF2α）是一个重要的真核起始因子，其作用是在真核翻译起始过程中介导起始tRNA（Met-tRNAi）与核糖体结合，作为一种内质网应激标志物，已被报道与各种癌症患者的预后有相关性。然而，关于p-eIF2α对乳腺癌尤其不同乳腺癌亚型的预后价值所知甚少。

　　2017年3月15日，英国《自然》旗下《科学报告》在线发表复旦大学附属肿瘤医院和上海医学院以及肿瘤医学协同创新中心的研究报告，发现p-eIF2α可预测三阴性乳腺癌患者的无病生存。

　　该队列回顾研究使用组织微阵列（来自乳腺癌女性患者233份肿瘤和配对肿瘤周围组织）进行了p-eIF2α免疫组化筛查。对染色结果进行半定量评分，对乳腺癌p-eIF2α表达水平及其潜在预后价值进行分析。

• 微阵列又称芯片，是将许多核酸片段、多肽、蛋白质或组织、细胞等生物样品有序地固化在惰性载体（玻片、硅片、尼龙膜等）表面组成高度密集二维阵列的微型生化反应和分析系统，是从一般阵列发展而来的点阵密度极高的阵列，包括基因、蛋白质、细胞和组织等微阵列。

　　结果发现，乳腺癌p-eIF2α水平显著上调（P＜0.001），p-eIF2α水平与淋巴结状态呈负相关（P=0.039）。

　　通过生存曲线（Kaplan-Meier）估算和比例风险模型（Cox回归）进行生存分析，发现p-eIF2α水平与无病生存较好有相关性（P=0.026）并且可以作为三阴性乳腺癌患者的独立预后因子（P=0.046）。

　　因此，该研究表明乳腺癌p-eIF2α上调，并且可以作为三阴性亚型患者预后的预测新指标。

　　该研究作者为郭亮、迟亚云、薛静彦、邵志敏、吴炅、等。

Sci Rep. 2017 Mar 15;7:44674.

Phosphorylated eIF2α predicts disease-free survival in triple-negative breast cancer patients.

Guo L, Chi Y, Xue J, Ma L, Shao Z, Wu J.

Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, PR China; Shanghai Medical College, Fudan University, Shanghai, PR China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), which functions as a marker of endoplasmic reticulum stress, has been reported to be associated with patient prognosis in various cancers. However, little is known about the prognostic value of p-eIF2α in breast cancer, particularly in different breast cancer subtypes. An immunohistochemistry screen for p-eIF2α was performed using a tissue microarray containing 233 tumors and paired peritumoral tissues from female patients diagnosed with breast cancer. The staining results were scored semiquantitatively, and the p-eIF2α expression level in breast cancer and its potential prognostic value were investigated. In this retrospective cohort study, we found that p-eIF2α levels were significantly upregulated in breast cancer (P<0.001). p-eIF2α level was negatively correlated with lymph node status (P=0.039). Survival analysis by Kaplan-Meier estimation and Cox regression showed that p-eIF2α level was correlated with better disease free survival (P=0.026) and served as an independent prognostic factor (P=0.046) in patients with triple-negative breast cancer. Our study revealed that p-eIF2α was upregulated in breast cancer and represented a novel predictor of prognosis in patients with triple-negative subtype.

PMID: 28294178

DOI: 10.1038/srep44674