Astrocyte Elevated Gene-1 is a Novel Prognostic Marker for Breast Cancer Progression and Overall Patient Survival

• Published in: Clinical cancer research Vol. 14; no. 11; pp. 3319 - 3326
• Main Authors: Li, Jun, Zhang, Nu, Song, Li-Bing, Liao, Wen-Ting, Jiang, Li-Li, Gong, Li-Yun, Wu, Jueheng, Yuan, Jie, Zhang, Hui-Zhong, Zeng, Mu-Sheng, Li, Mengfeng
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.06.2008
• Subjects: Adult; Antineoplastic agents; Astrocyte elevated gene-1; Biological and medical sciences; Biomarker; Biomarkers, Tumor - analysis; Blotting, Western; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cell Adhesion Molecules - biosynthesis; Disease Progression; Female; Gene Expression; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Mammary gland diseases; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Tumors; Human; Breast disease; Prognosis; Neuroglia; Biological marker; Breast cancer; Malignant tumor; Astrocyte; Survival; Mammary gland diseases; Gene; Tumor progression; Genetics; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-4054

Purpose: The present study was aimed at clarifying the expression of astrocyte elevated gene-1 ( AEG-1 ), one of the target genes of oncogenic Ha-ras, in breast cancer and its correlation with clinicopathologic features, including the survival of patients with breast cancer. Experimental Design: The expression of AEG-1 in normal breast epithelial cells, breast cancer cell lines, and in four cases of paired primary breast tumor and normal breast tissue was examined using reverse transcription-PCR and Western blot. Real-time reverse transcription-PCR was applied to determine the mRNA level of AEG-1 in the four paired tissues, each from the same subject. Furthermore, AEG-1 protein expression was analyzed in 225 clinicopathologically characterized breast cancer cases using immunohistochemistry. Statistical analyses were applied to test for the prognostic and diagnostic associations. Results: Western blot and reverse transcription-PCR showed that the expression level of AEG-1 was markedly higher in breast cancer cell lines than that in the normal breast epithelial cells at both mRNA and protein levels. AEG-1 expression levels were significantly up-regulated by up to 35-fold in primary breast tumors in comparison to the paired normal breast tissue from the same patient. Immunohistochemical analysis revealed high expression of AEG-1 in 100 of 225 (44.4%) paraffin-embedded archival breast cancer biopsies. Statistical analysis showed a significant correlation of AEG-1 expression with the clinical staging of the patients with breast cancer ( P = 0.001), as well as with the tumor classification ( P = 0.004), node classification ( P = 0.026), and metastasis classification ( P = 0.001). Patients with higher AEG-1 expression had shorter overall survival time, whereas patients with lower AEG-1 expression had better survival. Multivariate analysis suggested that AEG-1 expression might be an independent prognostic indicator for the survival of patients with breast cancer. Conclusions: Our results suggest that AEG-1 protein is a valuable marker of breast cancer progression. High AEG-1 expression is associated with poor overall survival in patients with breast cancer.