Journal article
EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer
Therapeutic advances in medical oncology, Vol.12, p.1758835920953731
2020
DOI: 10.1177/1758835920953731
PMID: 32973931
Abstract
Background: EGFR/c-Met activation/amplification and co-expression, mTOR upregulation/activation, and Akt/Wnt signaling upregulation have been individually associated with more aggressive disease and characterized as potential prognostic markers for lung cancer patients. Methods: Tumors obtained from 109 participants with stage I-IV non-small cell lung cancer (NSCLC) were studied for EGFR/c-Met co-localization as well as for total and active forms of EGFR, c-Met, mTOR, S6K, beta-catenin, and Axin2. Slides were graded by two independent blinded pathologists using a validated scoring system. Protein expression profile correlations were assessed using Pearson correlation and Spearman's rho. Prognosis was assessed using Kaplan-Meier analysis. Results: Protein expression profile analysis revealed significant correlations between EGFR/p-EGFR (p = 0.0412) and p-mTOR/S6K (p = 0.0044). Co-localization of p-EGFR/p-c-Met was associated with increased p-mTOR (p = 0.0006), S6K (p = 0.0018), and p-S6K (p < 0.0001) expression. In contrast, active beta-catenin was not positively correlated with EGFR/c-Met nor any activated proteins. Axin2, a negative regulator of the Wnt pathway, was correlated with EGFR, p-EGFR, p-mTOR, p-S6K, EGFR/c-Met co-localization, and p-EGFR/p-c-Met co-localization (allp-values <0.03). Kaplan-Meier analysis revealed shorter median survival in participants with high expression of Axin2, total beta-catenin, total/p-S6K, total/p-mTOR, EGFR, and EGFR/c-Met co-localization compared with low expression. After controlling for stage of disease at diagnosis, subjects with late-stage disease demonstrated shorter median survival when exhibiting high co-expression of EGFR/c-Met (8.1 monthversus22.3 month,p = 0.050), mTOR (6.7 monthversus22.3 month,p = 0.002), and p-mTOR (8.1 monthversus25.4 month,p = 0.004) compared with low levels. Conclusions: These findings suggest that increased EGFR/c-Met signaling is correlated with upregulated mTOR/S6K signaling, which may in turn be associated with shorter median survival in late-stage NSCLC.
Details
- Title: Subtitle
- EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer
- Creators
- Zachary D. Crees - University of Illinois Chicago, Rockford campusCaleb Shearrow - University of Illinois Chicago, Rockford campusLeo Lin - University of Illinois Chicago, Rockford campusJennifer Girard - University of Illinois Chicago, Rockford campusKavin Arasi - University of Illinois Chicago, Rockford campusAayush Bhoraskar - University of Illinois Chicago, Rockford campusJoseph Berei - University of Illinois Chicago, Rockford campusAdam Eckburg - University of Illinois Chicago, Rockford campusAustin D. Anderson - University of Illinois Chicago, Rockford campusChristian Garcia - University of Illinois Chicago, Rockford campusAriana Munger - University of Illinois Chicago, Rockford campusSunil Palani - University of Illinois Chicago, Rockford campusThomas J. Smith - Northern Illinois UniversityShylendra B. Sreenivassappa - OSF Saint Anthony Medical CenterConnie Vitali - University of Illinois Chicago, Rockford campusOdile David - University of Illinois ChicagoNeelu Puri - University of Illinois Chicago, Rockford campus
- Resource Type
- Journal article
- Publication Details
- Therapeutic advances in medical oncology, Vol.12, p.1758835920953731
- DOI
- 10.1177/1758835920953731
- PMID
- 32973931
- ISSN
- 1758-8340
- eISSN
- 1758-8359
- Publisher
- Sage
- Number of pages
- 15
- Grant note
- R21CA158965-01A1 / National Cancer Institute of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) I3736 / Community Foundation of Northern Illinois I3736 / Austrian Science Fund (FWF)
- Language
- English
- Date published
- 2020
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985218624802771
Metrics
1 Record Views