Astrocyte Elevated Gene-1 as a Novel Clinicopathological and Prognostic Biomarker for Gastrointestinal Cancers: A Meta-Analysis with 2999 Patients

Abstract

BackgroundThere have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients.MethodsWe performed a comprehensive search in PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct, Wiley Online Library, China National Knowledge Infrastructure (CNKI), WanFang and Chinese VIP databases. STATA 12.0 (STATA Corp., College, TX) was used to analyze the data extracted from suitable studies and Newcastle-Ottawa Scale was applied to assess the quality of included articles.ResultsThe current meta-analysis included 2999 patients and our results suggested that strong associations emerged between AEG-1 SI and histological differentiation (OR = 2.129, 95%CI: 1.377–3.290, P = 0.001), tumor (T) classification (OR = 2.272, 95%CI: 1.147–4.502, P = 0.019), lymph node (N) classification (OR = 2.696, 95%CI: 2.178–3.337, P<0.001) and metastasis (M) classification (OR = 3.731, 95%CI: 2.167–6.426, P<0.001). Furthermore, high AEG-1 SI was significantly associated with poor overall survival (OS) (HR = 2.369, 95%CI: 2.005–2.800, P<0.001) and deteriorated disease-free survival (DFS) (HR = 1.538, 95%CI: 1.171–2.020, P = 0.002). For disease-specific survival (DSS) and relapse-free survival (RFS), no statistically significant results were observed (HR = 1.573, 95%CI: 0.761–3.250, P = 0.222; HR = 1.432, 95%CI: 0.108–19.085, P = 0.786). Subgroup analysis demonstrated that high AEG-1 SI was significantly related to poor prognosis in esophageal squamous cell carcinoma (ESCC) (HR = 1.715, 95%CI: 1.211–2.410, P = 0.002), gastric carcinoma (GC) (HR = 2.255, 95%CI: 1.547–3.288, P<0.001), colorectal carcinoma (CRC) (HR = 2.922, 95%CI: 1.921–4.444, P<0.001), gallbladder carcinoma (GBC) (HR = 3.047, 95%CI: 1.685–5.509, P<0.001), hepatocellular carcinoma (HCC) (HR = 2.245, 95%CI: 1.620–3.113, P<0.001), pancreatic adenocarcinoma (PAC) (HR = 2.408, 95%CI: 1.625–3.568, P<0.001).ConclusionsThe current meta-analysis indicated that high AEG-1 SI might be associated with tumor progression and poor survival status in patients with gastrointestinal cancer. AEG-1 might play a vital role in promoting tumor aggression and could serve as a potential target for molecular treatments. Further clinical trials are needed to validate whether AEG-1 SI provides valuable insights into improving treatment decisions.

<p>Long Noncoding RNA DLGAP1-AS1 Promotes the Aggressive Behavior of Gastric Cancer by Acting as a ceRNA for microRNA-628-5p and Raising Astrocyte Elevated Gene 1 Expression</p>

“…27 AEG-1 is upregulated in GC, which is correlated with adverse clinical features and poor prognosis. [28][29][30] Functionally, AEG-1 performes cancer-promoting actions in gastric carcinogenesis and cancer progression, and is involved in multiple aggressive phenotype. [31][32][33][34][35] Yet, as far as we know, there has been no study that has explored the issue of DLGAP1-AS1, miR-628-5p, and AEG-1 in GC.…”

AEG-1 associates with metastasis in papillary thyroid cancer through upregulation of MMP2/9

“…Astrocyte-elevated gene-1 (AEG-1), also known as Metadherin or Lyric, was originally identified as a novel gene induced by human immunodeficiency virus (HIV)-1 or tumor necrosis factor (TNF)-α in primary human fetal astrocytes (PHFA) ( 5 , 6 ). Numerous recent studies have revealed that AEG-1 is markedly overexpressed in various types of human cancer, including hepatocarcinoma, gastrointestinal cancer and malignant glioma ( 7 , 8 ). AEG-1 played an important role in transformation, proliferation, cell survival, evasion of apoptosis, migration and invasion, metastasis, angiogenesis, chemoresistances and epithelial-mesenchymal transition ( 9 ).…”

Adenovirus-mediated anti-AEG-1 ScFv expression driven by stathmin promoter inhibits tumor growth in cervical cancer

“…Subsequently, it becomes increasingly hot in the field of tumor research, for the expression level of AEG-1 is abnormally high in various kinds of cancers [2][3][4] while extremely low in normal tissues, which suggests that AEG-1 may involve in tumorigenesis and represent a valuable biomarker. Further, many scientists have proposed that AEG-1 might be a novel prognostic marker on the basis of their investigating the correlation between the expression levels of AEG-1 and tumor samples with different clinical stages, whose studies supported that over-expression of AEG-1 was usually associated with lymph nodes/distant metastasis and a poor prognosis [5][6][7]. Importantly, loss and gain of function studies revealed that AEG-1 involved in multiple signal transduction pathways, and one of the most classic signal pathways was that PI3K-Akt and GSK-3β acted on Ha-ras to activate c-Myc, which subsequently induced AEG-1 to over-express and contributed to AEG-1 exerting its oncogenic properties [8].…”