Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer
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Published on: August 11, 2017
Shinobu Hosokawa1, Shinichi Toyooka, Yoshiro Fujiwara
1Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Purpose:
Translational approach is essentially needed to return the achievement of basic researches to oncological practice. The molecular associations among EGFR mutation and the components of EGFR signaling pathways have been extensively studied in laboratory experiments, although were still controversial. Moreover, the impact of downstream signaling of EGFR on clinical features in patients with non-small cell lung cancer (NSCLC) remains undetermined.
Patients And Methods:
A total of 93 surgically resected NSCLC patients were recruited the study. EGFR mutation status was analyzed by direct sequence method. The protein expression levels of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Akt (pAkt), and phosphorylated MAPK (pMAPK) were determined by immunohistochemistry.
Results:
There were 37 (40%) patients whose tumor harboring EGFR mutations (1 in exon 18, 22 in exon 19, and 14 in exon 21). Protein expression of EGFR, pEGFR, pAkt, and pMAPK was detected in 61 (66%), 27 (29%), 58 (62%), and 41 (44%) patients, respectively. The expression of pAkt was significantly associated with female gender and never-smoking history, and it was frequently upregulated in tumors harboring EGFR mutations (p<0.05, each). Phosphorylation of EGFR was closely correlated with the EGFR protein expression (p<0.05), but not with the EGFR mutations. In regard to patient survival, none of the molecular biomarkers was predictive for survival after surgical resection, but pMAPK expression was predictive for poor prognosis after gefitinib treatment in patients with postoperative recurrence (p<0.05), suggesting the strong linkage between pMAPK expression and survival benefit from gefitinib.
Conclusion:
Our result could provide new insight into MAP kinase signaling when we treat NSCLC patients with gefitinib.
Insights
This study investigated epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer (NSCLC). pMAPK expression predicted poor prognosis with gefitinib treatment, offering insights for NSCLC therapy.
Area of Science:
- Oncology
- Molecular Biology
- Translational Research
Background:
- The link between epidermal growth factor receptor (EGFR) mutations and signaling pathways in non-small cell lung cancer (NSCLC) requires further clarification.
- The impact of EGFR downstream signaling on clinical outcomes in NSCLC patients remains largely undetermined.
Purpose of the Study:
- To investigate the associations between EGFR mutations, downstream signaling pathway components, and clinical features in NSCLC.
- To explore the predictive value of molecular biomarkers for patient survival and treatment response in NSCLC.
Main Methods:
- Analyzed EGFR mutation status in 93 NSCLC patients using direct sequencing.
- Assessed protein expression of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Akt (pAkt), and phosphorylated MAPK (pMAPK) via immunohistochemistry.
Main Results:
- EGFR mutations were found in 40% of patients. pAkt expression correlated with female gender, never-smoking history, and EGFR mutations.
- pEGFR expression linked to EGFR protein levels but not mutations. No biomarkers predicted survival post-surgery.
- pMAPK expression predicted poor prognosis after gefitinib treatment in recurrent NSCLC patients.
Conclusions:
- pMAPK expression is linked to survival benefits from gefitinib in NSCLC patients.
- Findings offer insights into MAP kinase signaling for gefitinib treatment strategies in NSCLC.
