Prognostic value of amphiregulin and epiregulin mRNA expression in metastatic colorectal cancer patients
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Chen Jing1,*, Yang Han Jin2,*, Zhai You3, Qian Qiong1 and Zhou Jun3
1 Department of Medical Oncology, The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
2 Department of Pathology, The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
3 Department of Pharmacy, The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
* These authors have contributed equally to this work
Zhou Jun, email:
Keywords: metastatic colorectal cancer; amphiregulin; epiregulin; meta-analysis; prognostic biomarker
Received: April 11, 2016 Accepted: June 06, 2016 Published: June 17, 2016
Epidermal growth factor receptor (EGFR) and its ligands amphiregulin (AREG) and epiregulin (EREG) play a central role in the development of colorectal cancer, but the prognostic values of AREG and EREG are controversial. We conducted a meta-analysis of studies that investigated AREG and/or EREG mRNA levels in primary tumors to determine their prognostic value in metastatic colorectal cancer (mCRC). In addition, RAS status was assessed. Relevant articles were identified by searching the EMBASE, PubMed, and Cochrane Library databases. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated using a random-effects model. Nine studies involving 2167 patients were included in this meta-analysis. High AREG expression was associated with longer overall survival (OS) and progression-free survival (PFS). High EREG expression was also associated with prolonged OS and PFS. In RAS wild-type (WT) patients who received anti-EGFR therapy, high AREG and EREG expression was associated with longer OS. Our results indicate that high AREG and EREG mRNA expression are independent favorable prognostic biomarkers in mCRC. The expression of these ligands should be considered when evaluating prognoses in RAS-WT patients receiving anti-EGFR therapy.
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