Astrocyte elevated gene-1 is a novel prognostic marker for breast cancer progression and overall patient survival.
OBJECTIVE
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.


METHODS
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.
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China.
Jun
J
Li
Nu
N
Zhang
Li-Bing
LB
Song
Wen-Ting
WT
Liao
Li-Li
LL
Jiang
Li-Yun
LY
Gong
Jueheng
J
Wu
Jie
J
Yuan
Hui-Zhong
HZ
Zhang
Mu-Sheng
MS
Zeng
Mengfeng
M
Li
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008565:Membrane Proteins; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins