Over-expression of AEG-1 significantly associates with tumour aggressiveness and poor prognosis in human non-small cell lung cancer.
Astrocyte elevated gene 1 (AEG-1), a novel oncoprotein, has been implicated in oncogenesis and cancer progression in various types of human cancers. The clinical significance and biological role of AEG-1 in non-small cell lung cancer (NSCLC), however, remain unclear. In the present study, we found that the expression of AEG-1 was markedly up-regulated in NSCLC cell lines and NSCLC tissues at the level of both transcription and translation. Ectopically expressed AEG-1 enhanced the migratory and invasive abilities of NSCLC cells, whereas knockdown of endogenous AEG-1 by specific shRNAs significantly inhibited these abilities. The function of AEG-1 on metastasis modulation was associated with the activation of the PI3K-Akt and NF-kappaB signalling pathways. Furthermore, we showed high expression of AEG-1 in 99/200 (49.5%) paraffin-embedded archival NSCLC specimens. Moreover, statistical analysis displayed a significant correlation in AEG-1 expression with the clinical stage (p < 0.001), T classification (p = 0.001), N classification (p = 0.015), distant metastasis (p = 0.004) and differentiation (p = 0.027). Patients with higher AEG-1 expression had an overall shorter survival time, whereas patients with lower expression of AEG-1 had a better survival time. Multivariate analysis suggested that AEG-1 expression might be an independent prognostic indicator for the survival of NSCLC patients. Taken together, our results suggest that elevated expression of AEG-1 plays an important role in the aggressiveness of NSCLC, leading to a poor clinical outcome.
Song
Libing
L
State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong 510060, People's Republic of China. lb.song1@gmail.com
Li
Wen
W
Zhang
Huizhong
H
Liao
Wenting
W
Dai
Ting
T
Yu
Chunping
C
Ding
Xiaofan
X
Zhang
Lanjun
L
Li
Jun
J
D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011379:Prognosis; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D016601:RNA-Binding Proteins; C483039:MTDH protein, human