An EGFR signature predicts cell line and patient sensitivity to multiple tyrosine kinase inhibitors

Int J Cancer. 2020 Nov 1;147(9):2621-2633. doi: 10.1002/ijc.33053. Epub 2020 Jun 4.


EGFR is an oncogene with a high frequency of activating mutations in nonsmall cell lung cancer (NSCLC). EGFR inhibitors have been FDA-approved for NSCLC and have shown efficacy in patients with certain EGFR mutations. However, only 9% to 26% of these patients achieve objective responses. In our study, we developed an EGFR gene signature based on The Cancer Genome Atlas (TCGA) RNA-seq data of lung adenocarcinoma (LUAD) to direct the preselection of patients for more effective EGFR-targeted therapy. This signature infers baseline EGFR signaling pathway activity (denoted as EGFR score) in tumor samples, which is associated with tumor sensitivity to EGFR inhibitors and other tyrosine kinase inhibitors (TKIs). EGFR score predicted sensitivity of lung cancer cell lines to Erlotinib, Gefitinib and Sorafenib. Importantly, EGFR score calculated from pretreated samples was associated with patient response to Gefitinib and Sorafenib in lung cancer. Additionally, integration of the EGFR signature with TCGA LUAD data showed that it accurately predicted functional effects of different somatic EGFR mutations, and identified other mutations affecting EGFR pathway activity. Finally, using cancer cell line and clinical trial data, the EGFR score was associated with patient response to TKIs in liver cancer and other cancer types. The EGFR signature provides a useful biomarker that can expand the application of EGFR inhibitors or other TKIs and improve their treatment efficacy through patient stratification.

Keywords: EGFR; EGFR-targeted therapy; biomarker; tyrosine kinase inhibitor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant / methods
  • Datasets as Topic
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Erlotinib Hydrochloride / pharmacology
  • Erlotinib Hydrochloride / therapeutic use
  • Humans
  • Inhibitory Concentration 50
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Logistic Models
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Models, Genetic
  • Molecular Targeted Therapy / methods
  • Mutation
  • Predictive Value of Tests
  • Prognosis
  • Progression-Free Survival
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • RNA-Seq
  • Signal Transduction / genetics
  • Sorafenib / pharmacology
  • Sorafenib / therapeutic use
  • Transcriptome / genetics


  • Protein Kinase Inhibitors
  • Sorafenib
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors