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EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer.

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?

SUBMITTER: Crees ZD

PROVIDER: S-EPMC7493230 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer.

Crees Zachary D ZD Shearrow Caleb C Lin Leo L Girard Jennifer J Arasi Kavin K Bhoraskar Aayush A Berei Joseph J Eckburg Adam A Anderson Austin D AD Garcia Christian C Munger Ariana A Palani Sunil S Smith Thomas J TJ Sreenivassappa Shylendra B SB Vitali Connie C David Odile O Puri Neelu N

Therapeutic advances in medical oncology 20200914

<h4>Background</h4>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.<h4>Methods</h4>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-cate ...[more]

PMID: 32973931

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Project description:IntroductionTo compare the efficacy of silver in situ hybridization (SISH) and immunohistochemistry (IHC) in detecting MET and IGF1R alterations and to investigate their prevalence and prognostic significance. A possible correlation between MET receptor expression, MET gene alterations and the two most frequent occurring EGFR gene mutations was also investigated.Materials and methodsStage I to IIIA tumors from 326 patients with NSCLC were immunohistochemically tested for protein expression of MET and IGF-1. Their cytoplasmic expression was compared with the gene copy number of the MET and IGF1Rgenes by SISH in paraffin-embedded, formalin-fixed material. Correlations were made with the immunohistochemical expression of two frequent EGFR mutations and clinicopathological variables. Univariate and multivariate survival analyses was used to evaluate the prognostic efficacy of the tested markers.ResultsIn univariate analyses, high cytoplasmic MET expression showed a significant negative prognostic effect in adenocarcinoma patients (p = 0.026). MET gene to chromosome 7 ratio was a significant positive prognostic marker (p = 0.005), probably only due to the highly negative prognostic significance of chromosome 7 polysomy (p = 0.002). High IGF1R gene copy number was a negative prognostic marker for all NSCLC patients (p = 0.037). In the multivariate analysis, polysomy of chromosome 7 in tumor cells correlated significantly and independently with a poor prognosis (p = 0.011). In patients with adenocarcinoma, a high cytoplasmic MET expression was an independent negative prognostic marker (p = 0.013). In males a high IGF1R gene copy number to chromosome 15 count ratio was significantly and independently correlated to a poor prognosis (p = 0.018).ConclusionMET protein expression provides superior prognostic information compared with SISH. Polysomy of chromosome 7 is an independent negative prognostic factor in NSCLC patients. This finding has an important implication while examining genes located on chromosome 7 by means of SISH. High IGF1R gene copy number to chromosome 15 count ratio is an independent predictor of inferior survival in male patients with primary NSCLC.

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EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer.

Publications

EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer.

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