Overexpression of Endoplasmic Reticulum Oxidoreductin 1-alpha (ERO1L) Is Associated with Poor Prognosis of Gastric Cancer
CANCER RESEARCH AND TREATMENT
Authors: Seol, So-Young; Kim, Chul; Lim, Jae Yun; Yoon, Sun Och; Hong, Soon Won; Kim, Jong Won; Choi, Seung Ho; Cho, Jae Yong
Abstract
Purpose Gastric cancer is the second leading cause of cancer-related death worldwide. Although surgery is the standard curative treatmentfor gastric cancer, relapse occurs in a large number of patients, except in the case of early diagnosed gastric cancer. Following previous studies that identified endoplasmic reticulum oxidoreductin 1-alpha (ERO1L) as a potential marker for gastric cancer, we investigated the functional role of ERO1L in gastric cancer. Materials and Methods For validation of microarray data, the mRNA expression level of ERO1L was measured by quantitative real-time reverse transcription polymerase chain reaction in 56 independent stage III gastric cancer patients. Immunohistochemical staining was performed to examine the protein expression level of ERO1L in 231 gastric cancer patients. Correlation between gene expression and cancer prognosis was evaluated. Results Patients with high ERO1L expression had poorer survival than those with low expression (p < 0.01). Functional assays demonstrated that ERO1L knockdown inhibited cell proliferation, migration, invasion, and chemoresistance. In addition, involvement of inactivation of Akt and JNK signaling in molecular mechanisms of ERO1L inhibition was demonstrated. Conclusion High expression of ERO1L is associated with poor prognosis of patients with gastric cancer. These results indicate that ERO1L expression may be a clinically promising therapeutic target for prevention of gastric cancer.
Autophagy-related prognostic signature for breast cancer
MOLECULAR CARCINOGENESIS
Authors: Gu, Yunyan; Li, Pengfei; Peng, Fuduan; Zhang, Mengmeng; Zhang, Yuanyuan; Liang, Haihai; Zhao, Wenyuan; Qi, Lishuang; Wang, Hongwei; Wang, Chenguang; Guo, Zheng
Abstract
Autophagy is a process that degrades intracellular constituents, such as long-lived or damaged proteins and organelles, to buffer metabolic stress under starvation conditions. Deregulation of autophagy is involved in the progression of cancer. However, the predictive value of autophagy for breast cancer prognosis remains unclear. First, based on gene expression profiling, we found that autophagy genes were implicated in breast cancer. Then, using the Cox proportional hazard regression model, we detected autophagy prognostic signature for breast cancer in a training dataset. We identified a set of eight autophagy genes (BCL2, BIRC5, EIF4EBP1, ERO1L, FOS, GAPDH, ITPR1 and VEGFA) that were significantly associated with overall survival in breast cancer. The eight autophagy genes were assigned as a autophagy-related prognostic signature for breast cancer. Based on the autophagy-related signature, the training dataset GSE21653 could be classified into high-risk and low-risk subgroups with significantly different survival times (HR=2.72, 95% CI=(1.91, 3.87); P=1.37x10(-5)). Inactivation of autophagy was associated with shortened survival of breast cancer patients. The prognostic value of the autophagy-related signature was confirmed in the testing dataset GSE3494 (HR=2.12, 95% CI=(1.48, 3.03); P=1.65x10(-3)) and GSE7390 (HR=1.76, 95% CI=(1.22, 2.54); P=9.95x10(-4)). Further analysis revealed that the prognostic value of the autophagy signature was independent of known clinical prognostic factors, including age, tumor size, grade, estrogen receptor status, progesterone receptor status, ERBB2 status, lymph node status and TP53 mutation status. Finally, we demonstrated that the autophagy signature could also predict distant metastasis-free survival for breast cancer. (c) 2015 Wiley Periodicals, Inc.