Relationship between EGFR expression and subcellular localization with cancer development and clinical outcome
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Ge Yan1, Mohamed E.M. Saeed1, Sebastian Foersch2, Jose Schneider3, Wilfried Roth2 and Thomas Efferth1
1Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany
2Institute of Pathology, University Medical Center, Mainz, Germany
3Universidad Rey Juan Carlos, Facultad de Ciencias de la Salud, Móstoles, Spain
Thomas Efferth, email: [email protected]
Keywords: biomarker; oncogene; pathological parameters; prognosis; survival
Received: October 27, 2018 Accepted: February 15, 2019 Published: March 08, 2019
Epidermal growth factor receptor (EGFR) as a prevalent oncogene regulates proliferation, apoptosis and differentiation and thereby contributes to carcinogenesis. Even though, the documentation on its clinical relevance is surprisingly heterogeneous in the scientific literature. Here, we systematically investigated the correlation of mRNA to survival time and pathological parameters by analyzing 30 datasets in silico. Furthermore, the prognostic value of membrane-bound, cytoplasmic (mcEGFR) and nuclear expression (nEGFR) of EGFR was experimentally analyzed by immunohistochemical staining of 502 biopsies from 27 tumor types. We found that protein expression of EGFR showed better prognostic efficiency compared to mRNA, and that mcEGFR expression was positively correlated with nEGFR expression (p < 0.001). Unexpectedly, both mcEGFR and nEGFR expression were associated with low T stage (p < 0.001 and p = 0.004; respectively). Moreover, positive mcEGFR was significantly related to high differentiation (p = 0.027). No significant correlation was found with any other pathological parameters. Collectively, our results imply that the oncogenic function of EGFR may be more related to nascent stages of carcinogenesis than to advanced and progressive tumors, which may as well explain at least partially the occurrence of secondary resistance against EGFR-directed therapy.
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