Abstract
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.
Highlights
EIF2 comprises three subunits: α, β, and γ
Previous studies have reported detection of high p-eIF2αexpression levels in tumor samples compared with in matched noncancerous tissues, in cancers including bronchioloalveolar carcinomas of the lung[16], Hodgkin lymphoma[17], gastrointestinal carcinomas[18] and malignant melanoma[19]. Consistent with these previous findings, in this study, we found that p-eIF2αlevels are significantly higher in breast cancer than in peritumor tissues
P-eIF2αlevels reflect the severity of endoplasmic reticulum (ER) stress in tumors, indicating that ER stress plays an important role in the initiation of tumor formation
Summary
EIF2 comprises three subunits: α, β, and γ. The α-subunit of eIF2, eIF2α, can be phosphorylated on Ser[51], thereby effectively reducing the level of active eIF2. In this way, p-eIF2αcan significantly inhibit mRNA translation initiation[8] and global protein synthesis[9]. Evidence has mounted to demonstrate that p-eIF2αupregulation is associated with tumor development and progression[10,11,12]. The role of ER stress and UPR activation in the development of breast cancer, which has www.nature.com/scientificreports/. We investigate whether p-eIF2αcould serve as a prognostic biomarker in breast cancer, with a particular focus on differences between different molecular subtypes; and provide evidence for a new therapeutic target in breast cancer
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