Work

Artificial neural network systems to predict the response to sintilimab in squamous-cell non-small-cell lung cancer based on data of ORIENT-3 study

Year: 2024

Type: article

Abstract: Background: Existing biomarkers and models on predicting response to programmed cell death protein 1 monoclonal antibody in advanced squamous-cell non-small cell lung cancer (sqNSCLC) didn’t show enough accuracy. We used data of ORIENT-3 study to construct artificial neural network (ANN) systems to predict the response to sintilimab for sqNSCLC. Methods: Four ANN systems based on bulk RNA data to predict disease control (DC), immune DC (iDC), objective response (OR) and immune OR (iOR) were constructed and tested for patients with sqNSCLC treated with sintilimab. The mechanism exploration on the bulk and the spatial level were performed in patients from ORIENT-3 study and the real world, respectively. Findings: sqNSCLC patients with different responses to sintilimab showed each unique transcriptomic spectrum. Four ANN systems showed high accuracy in both the training cohort (AUC of DC, iDC, OR and iOR were 1.00, 1.00, 1.00 and 0.99, respectively) and the test cohort (AUC of DC, iDC, OR and iOR were 0.83, 0.89, 0.93 and 0.94, respectively). The performance of ANN systems were better than the according linear model systems, and showed high stability. The mechanism exploration on the bulk level suggested that patient with lower ANN system score (worse response) had higher ratio of immune-related pathways enrichment. The mechanism exploration on the spatial level suggested that patients with better response to immunotherapy had fewer clusters of both tumor and cytotoxicity T cell spots. Interpretation: The four ANN systems showed high accuracy, robustness and stability in predicting the response to sintilimab for patients with sqNSCLC. Funding: This work was supported by the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015). Declaration of Interest: None to declare. Ethical Approval: The designation of the cohort 3 was approved by the institutional review board of the Cancer Hospital, CAMS (No.23/262-4004). The study was performed in full accordance with the guidelines for Good Clinical Practice and the Declaration of Helsinki.

Source: Cancer Immunology Immunotherapy

DOI: 10.1007/s00262-024-03886-0

Authors: Tongji Xie, Guangyu Fan, Le Tang, Puyuan Xing, Yuankai Shi

Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Cancer Hospital of Chinese Academy of Medical Sciences

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,390