1. Predicting CTLA4 expression and prognosis in clear cell renal cell carcinoma using a pathomics signature of histopathological images and machine learning
- Author
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Xiaoqun Yang, Xiangyun Li, Haimin Xu, Silin Du, Chaofu Wang, and Hongchao He
- Subjects
Pathomics signature ,CTLA4 ,Machine learning ,Clear cell renal cell carcinoma ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Background: CTLA4, an immune checkpoint, plays an important role in tumor immunotherapy. The purpose of this study was to develop a pathomics signature to evaluate CTLA4 expression and predict clinical outcomes in clear cell renal cell carcinoma (ccRCC) patients. Methods: A total of 354 patients from the TCGA-KIRC dataset were enrolled in this study. The patients were stratified into two groups based on the level of CTLA4 expression, and overall survival rates were analyzed between groups. Pathological features were identified using machine learning algorithms, and a gradient boosting machine (GBM) was employed to construct the pathomics signatures for predicting prognosis and CTLA4 expression. The predictive performance of the model was subsequently assessed. Enrichment analysis was performed on diferentially expressed genes related to the pathomics score (PS). Additionally, correlations between PS and TMB, as well as immune infiltration profiles associated with different PS values, were explored. In vitro experiments, CTLA4 knockdown was performed to investigate its impact on cell proliferation, migration, invasion, TGF-β signaling pathway, and macrophage polarization. Results: High expression of CTLA4 was associated with an unfavorable prognosis in ccRCC patients. The pathomics signature displayed good performance in the validation set (AUC = 0.737; P
- Published
- 2024
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