Predicting Genomic Alterations of Phosphatidylinositol-3 Kinase Signaling in Hepatocellular Carcinoma: A Radiogenomics Study Based on Next-Generation Sequencing and Contrast-Enhanced CT

Background Exploring the genomic landscape of hepatocellular carcinoma (HCC) provides clues for therapeutic decision-making. Phosphatidylinositol-3 kinase (PI3K) signaling is one of the key pathways regulating HCC aggressiveness, and its genomic alterations have been correlated with sorafenib response. In this study, we aimed to predict somatic mutations of the PI3K signaling pathway in HCC samples through machine-learning-based radiomic analysis. Methods HCC patients who underwent next-generation sequencing and preoperative contrast-enhanced CT were recruited from West China Hospital and The Cancer Genome Atlas for model training and validation, respectively. Radiomic features were extracted from volumes of interest (VOIs) covering the tumor (VOI tumor ) and peritumoral areas (5 mm [VOI 5mm ], 10 mm [VOI 10mm ], and 20 mm [VOI 20mm ] from tumor margin). Factor analysis, logistic regression analysis, least absolute shrinkage and selection operator, and random forest analysis were applied for feature selection and model construction. Model performance was characterized based on the area under the receiver operating characteristic curve (AUC). Results A total of 132 HCC patients (mean age: 61.1 ± 14.7 years; 108 men) were enrolled. In the training set, the AUCs of radiomic signatures based on single CT phases were moderate (AUC 0.694–0.771). In the external validation set, the radiomic signature based on VOI 10mm in arterial phase demonstrated the highest AUC (0.733) among all models. No improvement in model performance was achieved after adding the tumor radiomic features or manually assessed qualitative features. Conclusions Machine-learning-based radiomic analysis had potential for characterizing alterations of PI3K signaling in HCC and could help identify potential candidates for sorafenib treatment.