2. Academic Validation
  3. Aberrant expression of MRAS and HEG1 as the biomarkers for osimertinib resistance in LUAD

Aberrant expression of MRAS and HEG1 as the biomarkers for osimertinib resistance in LUAD

  • Discov Oncol. 2024 Nov 19;15(1):678. doi: 10.1007/s12672-024-01552-6.
Mingxin Liu 1,  Bo Tang 2,  Run Xiang 1 3,  Peihong Hu 1,  Chuan Xu 2 4 5,  Lanlin Hu 6 7 8,  Qiang Li 9
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610042, China.
  • 2 Department of Oncology and Cancer Institute, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
  • 3 Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan University, Chengdu, 610042, China.
  • 4 Yu-Yue Pathology Scientific Research Center, Chongqing, 400039, China.
  • 5 Jinfeng Laboratory, Chongqing, 401329, China.
  • 6 Department of Oncology and Cancer Institute, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China. hulanlin@jflab.ac.cn.
  • 7 Yu-Yue Pathology Scientific Research Center, Chongqing, 400039, China. hulanlin@jflab.ac.cn.
  • 8 Jinfeng Laboratory, Chongqing, 401329, China. hulanlin@jflab.ac.cn.
  • 9 Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610042, China. liqiang@sichuancancer.org.
PMID: 39560891 DOI: 10.1007/s12672-024-01552-6
Abstract

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the most applied targeted therapy for EGFR-mutant lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, osimertinib, is widely used throughout lung Cancer treatment, with single or combination modes. One of the main barriers in osimertinib treatment is the acquired resistance and mechanisms are not fully understood. Gene expression Other than genetic mutations might predict drug response and mediate resistance occurrence. We analyzed six datasets of osimertinib-resistant LUAD cells from the Gene Expression Omnibus (GEO) database and identified two hub genes, named MRAS and HEG1. We found that the expression mode of MRAS/HEG1 in LUAD was osimertinib-dependent and contributed to drug resistance. We also explored potential mechanisms of hub genes related osimertinib resistance and emphasized the M2 infiltration involved. Moreover, potential therapeutic agents conquering MRAS/HEG1-related resistance were also identified. In conclusion, MRAS and HEG1 might be responsible for osimertinib resistance and could be promising prognostic biomarkers for osimertinib response in LUAD, which might provide insights into therapeutic strategies.

Keywords

Biomarker; Heart of glass 1 or EF-like domains 1 (HEG1); Lung adenocarcinoma (LUAD); Muscle RAS (MRAS); Osimertinib resistance.

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