A Geneformer-Based Model for Identifying Early Gastric Cancer Therapeutic Targets

Gastric cancer is a major global health issue characterized by high incidence and mortality rates. Early gastric cancer has a more favorable prognosis, yet most patients are diagnosed at an advanced stage due to subtle symptoms and limited diagnostic methods. Currently, the screening for therapeutic targets in early gastric cancer primarily relies on CRISPR-Cas9, next-generation sequencing, and advanced bioinformatics analysis, facing challenges such as off-target effects, high costs, complex data interpretation, and the elucidation of causal relationships. In this study, the Geneformer model was pre-trained on a large-scale corpus and fine-tuned on an early gastric cancer dataset to identify early gastric cancer cells. Potential therapeutic targets were identified through simulated gene perturbations and disease treatments, and their effectiveness was validated using KEGG pathway enrichment analysis and biological experimental results. After rigorous quality control and preprocessing of the data, the Geneformer model achieved excellent performance in the cell state annotation task, with an accuracy of 93.47% and an F1 score of 0.9187. Additionally, the model identified 445 potential therapeutic targets for early gastric cancer, such as TFF1, TFF2, and GKN2, which were enriched in gastric cancer-related pathways, with some targets validated by biological experiments. In summary, the proposed methodologies are capable of effectively identifying early gastric cancer cells and discovering potential therapeutic targets.