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

Abstract

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.

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

“…The proportion of positively stained cells and the staining intensity were higher in tumour tissues than in adjacent normal lung tissues. Our results are consistent with earlier studies, in that AEG-1 is over-expressed in many types of carcinomas, such as breast cancer, 7 prostate cancer, 9 cervical cancer 11 and hepatocellular carcinoma, 14 among others.…”

AEG-1 promotes mesenchymal transition through the activation of Rho GTPases in human glioblastoma cells

“…AEG-1 plays crucial roles in tumor progression such as transformation, survival, invasion, metastasis, angiogenesis and drug resistance in various types of human cancers (22)(23)(24)(25)(26)(27)(28). Furthermore, recent reports have revealed that AEG-1 participates in the regulation of the EMT process under diverse cellular conditions (29)(30)(31)(32)(33)(34)(35).…”

AEG-1 knockdown in colon cancer cell lines inhibits radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model

“…We speculate that the increased distant recurrence rate after radiation in high AEG-1 expressing tumors could be due to the metastasis promoting properties of AEG-1 [13]. AEG-1, also known as Metadherin (MTDH) and LYRIC, was originally identified as a human immunodeficiency virus-1 - inducible gene in human fetal astrocytes [14].…”