High Astrocyte Elevated Gene-1 Expression Research Articles

ELK3 Targeting AEG1 Promotes Migration and Invasion of Ovarian Cancer Cells under Hypoxia.

Ovarian cancer (OC) is one of the most common tumors in female reproductive organs with a five-year survival rate of less than 45%. Metastasis is a crucial contributor to OC development. ETS transcription factor (ELK3), as a transcriptional factor, have been involved in multiple tumor development. However, its role in OC remains elusive. In this study, we observed high expression of ELK3 and AEG1 in human OC tissues. OVCAR-3 and SKOV3 cells were treated with hypoxia to mimic tumor microenvironment in vivo. We found that the expression of ELK3 was significantly increased in cells under hypoxia compared with normoxia. ELK3 knockdown inhibited cell migration and invasion abilities under hypoxia. Moreover, ELK3 knockdown decreased β-catenin expression and inhibited the activation of Wnt/β-catenin pathway in SKOV3 cells under hypoxia. Astrocyte-elevated gene-1 (AEG1) has been reported to promote OC progression. Our results showed that the mRNA level of AEG1 was decreased when ELK3 knockdown under hypoxia. Dural luciferase assay confirmed that ELK3 bound to gene AEG1 promoter (-2005-+15) and enhanced its transcriptional activity under hypoxia. Overexpression of AEG1 increased the migration and invasion abilities of SKOV3 cell with ELK3 knockdown. In the absence of ELK3, the activation of β-catenin was recovered by AEG1 overexpression. To sum up, we conclude that ELK3 promotes AEG1 expression by binding to its promoter. ELK3 could promote migration and invasion of OC cells by targeting AEG1, which provides a potential basis for therapeutic approaches to OC.

Expression of astrocyte-elevated gene-1 indicates prognostic value of fluoropyrimidine-based adjuvant chemotherapy in resectable stage III colorectal cancer.

It is unclear which prognostic factor such as pathological features and gene mutation are majorly relevant for stage III disease and whether they aid in determining patients who will be benefit from postoperative adjuvant chemotherapy. The expression of astrocyte-elevated gene-1 (AEG-1), thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) was examined to investigate their role in adjuvant chemotherapy for patients with resectable stage III colorectal cancer (CRC). A significant positive correlation was observed between AEG-1, TS, ERCC1, EGFR, and VEGF gene expression levels in CRC cell lines, and low AEG-1 and TS expression were highly sensitive to 5-fluorouracil treatment. Our results showed that AEG-1 expression was high in T4 and caused CRC recurrence or metastasis. Patients with T4, high AEG-1, TS and VEGF expression had a significantly short disease-free survival and overall survival. In multivariate Cox regression analysis, high AEG-1 expression could be an independent prognostic factor indicating poor survival in patients with resectable stage III CRC treated with adjuvant chemotherapy. In conclusion, AEG-1 expression and tumor grade are potential prognostic factors for recurrence and survival in patients with stage III CRC receiving adjuvant fluoropyrimidine-based chemotherapy.

Abstract 353: Expression of astrocyte-elevated gene-1 is associated with prognostic value of adjuvant chemotherapy in resectable stage III colorectal cancer

Abstract Background: Administration of postoperative adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival for patients with resected colorectal cancer (CRC). Regarding the prognostic factors, including pathologic features and gene mutation have major relevance for stage III disease, it is not well known whether they might help select patients who would fare favorably when received adjuvant chemotherapy. OBJECTIVE: Expression of astrocyte-elevated gene-1 (AEG-1), thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) were needed to investigate the role involved in adjuvant combination therapy for patients with resectable stage III colon cancer. Methods: AEG-1, TS, ERCC1, EGFR and VEGF were investigated by CRC cell lines and intra-tumor immunohistochemistry stain. Furthermore, this study collected 29 patients with stage III colorectal cancer who underwent surgical resection from 2011 to 2016 and received postoperative adjuvant chemotherapy. The culmination of clinical data registration included surgical procedures, tumor size, number of lymph node metastases, and types of chemotherapy drugs. Result: A significant positive correlation between AEG-1, TS, ERCC1, EGFR, and VEGF gene expression levels were revealed in CRC cell lines. Cell lines with lower AEG-1 and TS expression had higher sensitivity to 5-FU treatment. In clinical studies, we found that higher AEG-1 expression was noted in T4 and also caused CRC recurrence or metastasis. Patients with T4 and stage IIIC CRC had a significantly shorter DFS (T4 v.s. T1-3, DFS, months, median: 4.1 ± 1.2 v.s. non-reach [NR], p < 0.001; IIIC v.s. IIIA or IIIB, DFS, months, median: 10.6 ± 5.3 v.s. NR, p = 0.037; respectively). Patients with higher AEG-1 and TS expression had a shorter DFS (AEG-1, high v.s. low, months, median: 12.8 ± 2.4 v.s. NR, p = 0.003; TS, high v.s. low, months, median: 13.8 ± 2.3 v.s. NR, p = 0.012; respectively). In multivariate Cox Regression analysis, advanced tumor invasion (T4) and high AEG-1 expression could be an independent prognostic factor to cause poor survival in resectable stage III CRC patients treated with adjuvant chemotherapy. Conclusion: Expressions of AEG-1 and tumor grade as a candidate prognostic factor of recurrence in stage III colorectal cancer patients receiving adjuvant fluoropyrimidine-based chemotherapy. A prospective cohort study should be guaranteed to validate these factors to be predictive markers of adjuvant chemotherapy benefit for stage III CRC. Citation Format: Chung-Yu Chen, Peng-Sheng Lai, Ying-Yin Chen, Long-Wei Lin. Expression of astrocyte-elevated gene-1 is associated with prognostic value of adjuvant chemotherapy in resectable stage III colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 353.

Expression of astrocyte elevated gene-1 protein in ameloblastomas, keratocystic odontogenic tumors, and dentigerous cysts.

Benign epithelial odontogenic tumors such as ameloblastoma and keratocystic odontogenic tumor (KCOT) may exhibit an aggressive clinical course reminiscent of malignancies. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1) is highly expressed in a variety of malignant neoplasms and its overexpression is associated with tumor invasion, metastasis, and poor survival. However, the role of AEG-1 in odontogenic tumors and cysts is still undiscovered. Immunohistochemical staining of AEG-1 was performed in 42 cases of ameloblastoma, 29 cases of KCOT, and 19 cases of dentigerous cyst. Correlations between AEG-1 expression and clinical parameters of ameloblastomas or KCOTs were statistically analyzed. AEG-1-positive staining was found in 37 (88%) of 42 ameloblastomas and in 24 (83%) of 29 KCOTs. None of 19 dentigerous cysts were positive for AEG-1 protein. For ameloblastomas, AEG-1 protein expression was significantly higher in ameloblast-like cells than in stellate reticulum-like cells (P = 0.003). For KCOTs, AEG-1 protein was diffusely expressed in all lining epithelial cells except the superficial parakeratinized cells. Moreover, the frequency of cortical plate perforation was significantly higher in ameloblastomas with high AEG-1 expression than in ameloblastomas with low or negative AEG-1 expression (P = 0.043). Significantly higher expression of AEG-1 protein in ameloblastomas and KCOTs than in dentigerous cysts and significantly greater frequency of cortical plate perforation in high AEG-1-expressed ameloblastomas than in low or negative AEG-1-expressed ameloblastomas may imply the high potential of AEG-1 to serve as a locally invasive biomarker and a target for novel therapy.

The expression of astrocyte elevated gene-1 in human non-small-cell lung cancer and its relationship with postoperative chemotherapy and radiotherapy.

To examine the expression of astrocyte elevated gene-1 (AEG-1) in non-small-cell lung cancer (NSCLC) and analyse the correlation between AEG-1 expression and the prognosis of the patients, particularly the relationship between AEG-1 expression and postoperative chemotherapy and radiotherapy. The expression of AEG-1 was analysed by immunohistochemistry in 225 primary NSCLC specimens and 42 adjacent normal lung tissue specimens. Statistical analyses were performed to evaluate the correlation between AEG-1 expression and the clinicopathological characteristics of the patients as well as the predictive value of AEG-1. The expression of AEG-1 was associated with the pathological stage (P < 0.001) and lymph node status (P = 0.028). A multivariate analysis indicated that AEG-1 expression was an independent prognostic factor for both overall survival (OS) and disease-free survival (DFS). In the postoperative chemotherapy group, the OS (P = 0.014) and DFS (P = 0.009) in the low AEG-1 expression group were longer than the survival times in the high AEG-1 expression group. In the postoperative radiotherapy group, the local recurrence-free survival was significantly shorter in patients whose tumours showed high AEG-1 expression (P = 0.016). AEG-1 expression could be a predictor for OS and DFS in NSCLC patients. Patients with low AEG-1 expression received the greatest benefit from both postoperative chemotherapy and radiotherapy.

Abstract 4897: Genetic variants and expression of AEG-1 in relation to clinical outcome and radiotherapy response in colorectal cancer patients and cell lines

Abstract Background: Colorectal cancer (CRC) is the third most common cancer in men and the second in woman worldwide. The therapy of CRC has been critically improved during the past two decades, but the treatment response varies significantly between different treatments and patients. Therefore it is of need to search for biomarkers for more suitable prognosis and treatment. The aim of this study was to investigate genetic variants of the astrocyte elevated gene-1 (AEG-1), its expression in CRC patient samples and colon cancer cell lines and the potential correlation to clinicopathological variables and treatment response. Materials and Methods: We analysed genetic variants and the mRNA and protein expression of AEG-1 in 593 CRC patient samples by direct Sanger sequencing, qPCR and immunohistochemistry. Of the patients, 158 rectal cancer patients were enrolled in the Swedish clinical trial of preoperative radiotherapy (RT). AEG-1 expression in response to γ-irradiation was analysed by Western blot in 5 colon cancer cell lines. We inhibited the AEG-1 expression by siRNA in the cell lines, and their survival was analysed after γ-irradiation. Results: By direct sequencing we found 29 variants, of which 12 were novel. Six of the variants were exonic and 23 intronic. The variant c.1353G&amp;gt;A, rs2331652 was found only in 4 samples and the variant c.1679-6 T&amp;gt;C in only one sample. In the cell lines KM12C, KM12SM and KM12L4a we found a deletion in exon 4 (c.595_598delAGAG). AEG-1 mRNA and protein expression revealed a significant increased AEG-1 expression in the primary tumors and metastases compared to the normal mucosa in all patient cohorts (p&amp;lt;0.006) and on the mRNA level a higher expression in tumors located in the rectum compared to tumors in the colon (p=0.047). In the rectal cancer patients from the Swedish trail of preoperative RT, a high AEG-1 expression correlated with a higher risk of distant recurrence and disease free survival (p=0.001 respectively) independently of the tumor stage, only in patients receiving preoperative RT. AEG-1 knock-down in the radioresistant cell lines KM12L4a, SW480 and SW620 resulted in reduction of the survival after radiation, but not in the radiosensitive cell lines KM12C and HCT116. The AEG-1 expression was up-regulated shortly after 2 Gy γ-radiation in KM12C, KM12L4a and SW480, but not in SW620 and HCT116. Conclusion: We found several novel AEG-1 variants. The AEG-1 expression at the mRNA and/or protein level was up-regulated in the primary tumour and metastases compared to the normal mucosa. Furthermore we showed for the first time that the AEG-1 expression is an independent prognostic factor for distant recurrence and disease-free survival in rectal cancer patients after treatment with preoperative RT. The cell line studies suggest AEG-1 as a promising radiosensitizing target for rectal cancer. Citation Format: Sebastian Gnosa, Veronika Patcha Brodin, Ivana Ticha, Gunnar Adell, Gunnar Arbman, Hong Zhang, Xiao-Feng Sun. Genetic variants and expression of AEG-1 in relation to clinical outcome and radiotherapy response in colorectal cancer patients and cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4897. doi:10.1158/1538-7445.AM2014-4897

AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial.

Background:Preoperative radiotherapy (RT) is widely used to downstage rectal tumours, but the rate of recurrence varies significantly. Therefore, new biomarkers are needed for better treatment and prognosis. It has been shown that astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and treatment resistance. Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties.Methods:The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay.Results:The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT (P<0.01). High AEG-1 expression in the primary tumour of the patients treated with RT correlated independently with higher risk of distant recurrence (P=0.009) and worse disease-free survival (P=0.007). Downregulation of AEG-1 revealed a decreased survival after radiation in radioresistant colon cancer cell lines.Conclusions:The AEG-1 expression was independently related to distant recurrence and disease-free survival in rectal cancer patients with RT and could therefore be a marker to discriminate patients for distant relapse.

AEG-1 is associated with tumor progression in nonmuscle-invasive bladder cancer.

Astrocyte elevated gene-1 (AEG-1), a novel oncoprotein, has been implicated in oncogenesis and cancer progression in various types of human cancers. Here, immunohistochemistry was used to detect AEG-1 expression in nonmuscle-invasive bladder cancer (NMIBC), and these data were examined for correlation with clinicopathological parameters, and prognosis. Immunohistochemical analysis revealed that AEG-1 expression was significantly higher in bladder cancer tissues than that in normal tissues. High expression of AEG-1 was found in 45 % of bladder cancers and significantly associated with tumor grade (P = 0.002) and progression (P = 0.028). The Kaplan-Meier survival analysis demonstrated that AEG-1 expression was significantly associated with shorter progression-free survival (P = 0.0011). Multivariate analysis further demonstrated that AEG-1 was an independent prognostic factor for patients with BC. AEG-1 protein may contribute to the malignant progression of bladder cancer, and present as a novel marker to predict the progression of NMIBC.

Expression of astrocyte elevated gene-1 closely correlates with the angiogenesis of gastric cancer.

Previous studies have demonstrated that astrocyte elevated gene-1 (AEG-1) is overexpressed in several cancer types and that its upregulation may promote cell proliferation, cell transformation and tumor progression. The present study investigated the expression and prognostic value of AEG-1 in primary gastric cancer (GC) as well as its role in angiogenesis. The results obtained from real-time reverse transcription polymerase chain reaction and western blotting revealed the upregulation of AEG-1 mRNA (P=0.007) and protein expression (P<0.001) in the majority of cancerous tissues compared with matched adjacent non-cancerous gastric tissues. To further investigate the clinicopathological and prognostic roles of AEG-1, immunohistochemical analysis of 216 GC tissue blocks was performed. The results showed that high AEG-1 expression closely correlated with differentiation degree (P<0.001 ), T stage (P<0.001), N stage (P=0.003) and M stage (P=0.013). Consistent with the abovementioned results, AEG-1 upregulation was also found to significantly correlate with poor survival in GC patients (P<0.001). Furthermore, carcinomas with elevated AEG-1 expression demonstrated high vascular endothelial growth factor (VEGF) expression and microvessel density, which was labeled by cluster of differentiation 34. In addition, an AEG-1 siRNA assay in MGC-803 cells showed that the AEG-1 gene may promote VEGF and hypoxia-inducible factor-1α protein and mRNA expression. The results of the current study indicated that AEG-1 may serve as a valuable prognostic marker for GC and may be involved in regulating tumor angiogenesis.

Expression of AEG-1 and microvessel density correlates with metastasis and prognosis of oral squamous cell carcinoma

Astrocyte elevated gene 1 (AEG-1) expression is up-regulated in various human cancers and plays an important role in tumorigenesis and progression. The aim of this study was to explore AEG-1 expression in oral squamous cell carcinoma (OSCC) and to assess whether it is associated with microvessel density (MVD), metastasis, and survival. Specimens from 87 patients with OSCC were investigated by immunohistochemistry staining for AEG-1 and MVD. By statistical analysis, we studied the correlations between the expression of AEG-1 and MVD and various clinicopathological factors, including overall survival (OS). We found that AEG-1 was highly expressed in 51.72% of OSCC. Expression was closely correlated with differentiation, clinical stage, T classification, and lymph node metastasis. The MVD had similar results. Expression of AEG-1 correlated positively with MVD. The lymph node metastatic rate in patients with high AEG-1/high MVD was significantly higher than in patients with high AEG-1/low MVD, low AEG-1/high MVD, or low AEG-1/low MVD. Patients with high AEG-1 expression showed far lower OS rates than those with low expression. For MVD, there were similar results. Only AEG-1 and MVD expression were independent prognostic factors for OS by multivariate analysis. Expression of AEG-1 may be correlated with tumor angiogenesis and metastasis and is a valuable prognostic factor in patients with OSCC.

High expression of astrocyte elevated gene-1 (AEG-1) is associated with progression of cervical intraepithelial neoplasia and unfavorable prognosis in cervical cancer

BackgroundAstrocyte elevated gene-1(AEG-1) plays an important role in the development and progression of certain types of human cancers. However, the expression dynamics of AEG-1 in cervical cancer and its clinical/prognostic significance are unclear.MethodIn present study, the methods of tissue microarrays (TMA) and immunohistochemistry (IHC) were utilized to investigate AEG-1 expression in cervical intraepithelial neoplasia (CIN) and cervical cancer. Receiver operating characteristic (ROC) curve analysis, χ2 test, Kaplan-Meier plots, and multivariate Cox regression analysis were used to analyze the data.ResultsThe expression level of AEG-1 was increased from CIN I to CIN III. High expression of AEG-1 could be observed in 61.1% (55/90) of cervical cancer. Moreover, high expression of AEG-1 correlated with tumor size and lymph node metastasis (all P <0.05). More importantly, high expression of AEG-1 was closely associated with cervical cancer patient shortened survival time as evidenced by univariate and multivariate analysis (P <0.05).ConclusionsOur data suggest for the first time that high expression of AEG-1 is associated significantly with progression of cervical cancer. AEG-1 overexpression, as examined by IHC, has the potential to be used as an immunomarker to predict prognosis of cervical cancer patients.

AEG-1 is associated with clinical outcome in neuroblastoma patients

Astrocyte elevated gene 1 (AEG-1), a novel gene that was cloned in 2002, has emerged in recent years as a potentially crucial mediator of tumor malignancy and aberrant elevation of AEG-1 expression frequently occurs in several human cancers, including breast cancer, prostate cancer, gastric cancer. However, whether AEG-1 deregulation also occurs in neuroblastoma remains unclear. In previous study we reported that AEG-1 was over expressed in neuroblastoma cell lines and knockdown of AEG-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells. In this study, we investigated the expression of AEG-1 and evaluate its prognostic significance by correlating AEG-1 expression levels with clinic pathologic features and survival in 32 archived neuroblastoma patients We found that positive AEG-1 immunoreactivities were present in all neuroblastoma cases, 75% showed high expression of AEG-1. And high expression of AEG-1 was commonly seen in vascular endothelial cells and glandula in neuroblastoma samples. AEG-1 expression was strongly correlated with age at diagnosis (P=0.012), clinical stage (P=0.030) and tumor histology stage (P=0.041). However, our analyses did not show significant associations between AEG-1 expression and other clinical features including gender and primary tumor site. Importantly, our data presented in this report provide, for the first time, evidence that elevated expression of AEG-1 protein is correlated with poor prognosis and reduced survival of patients with neuroblastoma (P= 0.031). Overall, the data support the notion that AEG-1 might be used as a biomarker for neuroblastoma patients.

Clinical Significance of Astrocyte Elevated Gene-1 Expression in Human Epithelial Ovarian Carcinoma

Astrocyte elevated gene-1 (AEG-1) plays an important role in tumor progression including transformation, evasion of apoptosis, invasion, metastasis, and chemoresistance. However, the expression of AEG-1 in ovarian carcinoma and its significance are still unclear. The aim of this study was to examine the expression of AEG-1 in ovarian carcinoma. Immunohistochemistry was performed to determine the expression of AEG-1 in 81 ovarian carcinoma specimens. The correlation of AEG-1 expression with clinicopathological parameters was assessed using χ2 analysis. Patient survival was analyzed using the Kaplan-Meier and log-rank tests. Cox regression was used for the multivariate analysis of prognostic factors. High expression of AEG-1 was detected in 66.67% of the ovarian carcinomas and was significantly associated with the International Federation of Gynecology and Obstetrics stage, histological grade, presence of residual tumor after primary surgery, and tumor recurrence. Patients with high AEG-1 expression had significantly poorer overall survival and disease-free survival (both P<0.001) when compared with patients with low expression of AEG-1. The multivariate Cox analysis showed that AEG-1 was an independent factor for both overall survival and disease-free survival (both P<0.001). These results showed that high AEG-1 expression was associated with progression and prognosis of ovarian carcinoma.

Expression of Astrocyte Elevated Gene-1

To assess the expression of astrocyte elevated gene-1 (AEG-1) in different endometrial specimens and to investigate its relationship with clinicopathological features and its impact on patient outcome. By Western blot analysis, we investigated AEG-1 expression in paired endometrial tissues and adjacent nontumor tissues of the same patients (n = 4). Immunohistochemistry analysis was used to determine the expression levels of AEG-1 protein in 35 normal endometrium, 40 atypical endometrial hyperplasia, and 174 endometrial cancers. The correlation between AEG-1 expression and various clinicopathological characteristics of endometrial cancer patients was analyzed. Western blot analysis showed that AEG-1 expression levels were up-regulated in all 4 human primary endometrial cancer tissues compared with their matched adjacent noncancerous tissues. The frequent and strong expression of AEG-1 was gradually elevated in normal endometrial tissue, atypical hyperplasia, and endometrial cancers (P < 0.001). Although AEG-1 staining mainly emerged in the cytoplasm, a nuclear distribution was observed in both invasive and advanced endometrial cancer cells. The Ki67 (a proliferation marker) was frequently expressed in the high AEG-1-expressed area, whereas areas with low AEG-1 levels showed weak Ki67 expression. Astrocyte elevated gene-1 overexpression was positively correlated with the International Federation of Gynecology and Obstetrics stage, depth of myometrial invasion, lymph node metastasis, lymph vascular space invasion, and recurrence but not with age or histological type. Patients with high AEG-1 expression had significantly poor overall survival and disease-free survival compared with patients with AEG-1 low expression (both P < 0.001). Multivariate Cox proportional hazards regression demonstrated that high AEG-1 expression was an independent prognostic factor for both the overall survival and disease-free survival of patients with endometrial cancer (P = 0.002 and P = 0.004, respectively). Astrocyte elevated gene-1 overexpression may be associated with carcinogenesis and tumor progression in endometrial cancer. Moreover, it may be a new prognostic marker or a target for improving the treatment efficiency of patients with endometrial cancer.

Prognostic significance of AEG-1 expression in colorectal carcinoma

Astrocyte elevated gene-1 (AEG-1), as an HIV-1 or TNF-alpha-inducible transcript, is associated with various aspects of tumor malignancy. However, relatively little knowledge is available related to the role of AEG-1 in colorectal carcinoma. By immunohistochemical and western blot analysis, we investigated AEG-1 expression in normal mucosa, adenomas, and carcinomas of colorectum. By statistical analysis, we determined its relationship with clinicopathological parameters and overall survival in colorectal carcinoma. We found that AEG-1 expression levels were gradually elevated in normal tissues, low-grade adenoma, high-grade adenoma, and colorectal carcinoma, respectively. Though AEG-1 staining mainly emerged in the cytoplasm, we observed that nuclear staining of AEG-1 tends to become more common in lesions from patients with more advanced disease stages. Furthermore, there was a similar trend for Ki67 expression (as a proliferative index) from normal mucous to adenoma and carcinoma. Statistical analysis revealed that AEG-1 expression was markedly correlated with the UICC stage (P < 0.001), T classification (P = 0.002), N classification (P = 0.015), M classification (P = 0.010), Ki67 expression (P = 0.012), and histological differentiation (P = 0.037) in the colorectal cancer patients. Besides, those patients with high AEG-1 levels had shorter survival time (P < 0.001). High AEG-1 expression correlates with poor overall survival in the colorectal carcinoma patients. In addition, AEG-1 expression in colorectal carcinoma may be associated with tumor progression, indicating that AEG-1 may be a potential preventive and chemotherapeutic target in the patients.

Clinical significance of astrocyte elevated gene-1 expression in human oligodendrogliomas

Objective To investigate the expression of astrocyte elevated gene-1 (AEG-1) in human oligodendrogliomas and the association between AEG-1 expression and progression of oligodendrogliomas. Methods The expression of AEG-1 in normal human oligodendroglial cells, oligodendroglioma cell line, and four pairs of matched oligodendroglioma tissues and their adjacent normal brain tissues was detected by quantitative RT-PCR and western blotting. In addition, AEG-1 protein expression was examined in 75 cases of histologically characterized oligodendrogliomas by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. Results Western blotting and RT-PCR showed that AEG-1 mRNA and protein were elevated in the oligodendroglioma cell line and significantly upregulated in primary oligodendrogliomas compared with the adjacent non-cancerous brain tissues. Immunohistochemical analysis showed that 51 of 75 (68.0%) paraffin-embedded archival oligodendroglioma samples exhibited high expression of AEG-1. Statistical analysis suggested that upregulation of AEG-1 was significantly correlated with the histological grade of oligodendroglioma ( p = 0.000) and that patients with high AEG-1 level exhibited shorter survival time ( p = 0.000). Multivariate analysis revealed that AEG-1 upregulation might be an independent prognostic indicator for the survival of patients with oligodendroglioma. Conclusions AEG-1 might represent a novel, useful diagnostic and prognostic marker for oligodendroglioma and play a role during the development and progression of the disease.

Overexpression of AEG-1 in renal cell carcinoma and its correlation with tumor nuclear grade and progression

The study was aimed at detecting the expression of a newly found oncogene, astrocyte elevated gene-1 (AEG-1), in renal cell carcinoma (RCC) and its correlation with histopathologic features and the survival of patients. Real-time reverse transcription-PCR and Western blot showed markedly higher expression of AEG-1 in 8 cases of RCC tissue compared with the paired normal tissue from the same patient. The expression level of AEG-1 was also increased in four RCC cell lines in contrast with normal tubular epithelial human kidney cells 2 (HK-2) at both mRNA and protein levels. Furthermore, immunohistochemistry analysis showed highly expressed AEG-1 in 96 of 102 (94.1%) cases of paraffin-embedded archival RCC tissue. Statistical analysis showed a significant correlation of AEG-1 expression with tumor grade (P <0.001), clinical staging (P = 0.003), T classification (P = 0.003) as well as metastasis classification (P=0.032). The means for survival time of low AEG-1 expression group was 76.98m<br />while high AEG-1expression group was 60.94m. Our results suggest that AEG-1 protein is overexpressed in RCC and plays an important role in tumor differentiation and progression. <br />High AEG-1 expression is closely associated with poor prognosis. Astrocyte elevated gene-1, AEG-1, renal cell carcinoma, prognosis.

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.

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

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. 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. 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. 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.