Non-invasive identification of TKI-resistant NSCLC: a multi-model AI approach for predicting EGFR/TP53 co-mutations.

Authors

Li J,Xu R,Wang D,Liang Z,Li Y,Wang Q,Bi L,Qi Y,Zhou Y,Li W

Affiliations (8)

  • Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Guo Xue Xiang 37, Chengdu, Sichuan, 610041, China.
  • Institute of Respiratory Health, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. [email protected].
  • Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Guo Xue Xiang 37, Chengdu, Sichuan, 610041, China. [email protected].
  • Institute of Respiratory Health, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [email protected].
  • Precision Medicine Center, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [email protected].
  • The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu, Sichuan, China. [email protected].

Abstract

To investigate the value of multi-model based on preoperative CT scans in predicting EGFR/TP53 co-mutation status. We retrospectively included 2171 patients with non-small cell lung cancer (NSCLC) with pre-treatment computed tomography (CT) scans and predicting epidermal growth factor receptor (EGFR) gene sequencing from West China Hospital between January 2013 and April 2024. The deep-learning model was built for predicting EGFR / tumor protein 53 (TP53) co-occurrence status. The model performance was evaluated by area under the curve (AUC) and Kaplan-Meier analysis. We further compared multi-dimension model with three one-dimension models separately, and we explored the value of combining clinical factors with machine-learning factors. Additionally, we investigated 546 patients with 56-panel next-generation sequencing and low-dose computed tomography (LDCT) to explore the biological mechanisms of radiomics. In our cohort of 2171 patients (1,153 males, 1,018 females; median age 60 years), single-dimensional models were developed using data from 1,055 eligible patients. The multi-dimensional model utilizing a Random Forest classifier achieved superior performance, yielding the highest AUC of 0.843 for predicting EGFR/TP53 co-mutations in the test set. The multi-dimensional model demonstrates promising potential for non-invasive prediction of EGFR and TP53 co-mutations, facilitating early and informed clinical decision-making in NSCLC patients at risk of treatment resistance.

Topics

Carcinoma, Non-Small-Cell LungLung NeoplasmsTumor Suppressor Protein p53Drug Resistance, NeoplasmProtein Kinase InhibitorsJournal Article

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