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Relationship between EGFR expression and subcellular localization with cancer development and clinical outcome
Ge Yan1, Mohamed E M Saeed1, Sebastian Foersch2
1Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
Oncotarget
|April 9, 2019
Summary
Epidermal growth factor receptor (EGFR) protein expression, particularly membrane-bound, cytoplasmic (mcEGFR), correlates with early cancer stages and high differentiation, suggesting its role in initial carcinogenesis rather than advanced tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Epidermal growth factor receptor (EGFR) is a known oncogene implicated in cell proliferation, apoptosis, and differentiation, contributing to cancer development.
- The clinical relevance of EGFR in various cancers is inconsistently reported in scientific literature, necessitating further investigation.
Purpose of the Study:
- To systematically investigate the correlation between EGFR mRNA levels and patient survival and pathological parameters using in silico analysis.
- To experimentally determine the prognostic value of membrane-bound, cytoplasmic EGFR (mcEGFR) and nuclear EGFR (nEGFR) expression in a large cohort of tumor biopsies.
Main Methods:
- In silico analysis of 30 datasets to correlate EGFR mRNA expression with survival and pathological data.
- Immunohistochemical staining of 502 biopsies from 27 tumor types to assess mcEGFR and nEGFR protein expression.
- Statistical analysis to evaluate correlations between EGFR expression levels and clinicopathological parameters.
Main Results:
- EGFR protein expression demonstrated superior prognostic efficiency compared to mRNA levels.
- Positive correlation observed between mcEGFR and nEGFR expression (p < 0.001).
- Both mcEGFR and nEGFR expression were unexpectedly associated with lower T stages (p < 0.001 and p = 0.004, respectively) and mcEGFR with higher differentiation (p = 0.027).
Conclusions:
- EGFR's oncogenic function appears more prominent in the early stages of carcinogenesis than in advanced or progressive tumors.
- These findings may offer partial explanation for the development of secondary resistance to EGFR-targeted therapies.
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