ABSTRACT
PURPOSE: To establish a pathomic model using histopathological image features for predicting indoleamine 2,3-dioxygenase 1 (IDO1) status and its relationship with overall survival (OS) in breast cancer. METHODS: A pathomic model was constructed using machine learning and histopathological images obtained from The Cancer Genome Atlas database to predict IDO1 expression. The model performance was evaluated based on the area under the curve, calibration curve, and decision curve analysis (DCA). Prediction scores (PSes) were generated from the model and applied to divide the patients into two groups. Survival outcomes, gene set enrichment, immune microenvironment, and tumor mutations were assessed between the two groups. RESULTS: Survival analysis followed by multivariate correction revealed that high IDO1 is a protective factor for OS. Further, the model was calibrated, and it exhibited good discrimination. Additionally, the DCA showed that the proposed model provided a good clinical net benefit. The Kaplan-Meier analysis revealed a positive correlation between high PS and improved OS. Univariate and multivariate Cox regression analyses demonstrated that PS is an independent protective factor for OS. Moreover, differentially expressed genes were enriched in various essential biological processes, including extracellular matrix receptor interaction, angiogenesis, transforming growth factor ß signaling, epithelial mesenchymal transition, cell junction, tryptophan metabolism, and heme metabolic processes. PS was positively correlated with M1 macrophages, CD8 + T cells, T follicular helper cells, and tumor mutational burden. CONCLUSION: These results indicate the potential ability of the proposed pathomic model to predict IDO1 status and the OS of breast cancer patients.
Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Indoleamine-Pyrrole 2,3,-Dioxygenase , Machine Learning , Tumor Microenvironment , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Breast Neoplasms/metabolism , Female , Prognosis , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Middle Aged , Gene Expression Regulation, Neoplastic , Kaplan-Meier EstimateABSTRACT
This study utilizes the genetic algorithm (GA) and Levenberg-Marquardt (L-M) algorithm to optimize the parameter acquisition process for two commonly used viscoelastic models: 2S2P1D and Havriliak-Negami (H-N). The effects of the various combinations of the optimization algorithms on the accuracy of the parameter acquisition in these two constitutive equations are investigated. Furthermore, the applicability of the GA among different viscoelastic constitutive models is analyzed and summarized. The results indicate that the GA can ensure a correlation coefficient of 0.99 between the fitting result and the experimental data of the 2S2P1D model parameters, and it is further proved that the fitting accuracy can be achieved through the secondary optimization via the L-M algorithm. Since the H-N model involves fractional power functions, high-precision fitting by directly fitting the parameters to experimental data is challenging. This study proposes an improved semi-analytical method that first fits the Cole-Cole curve of the H-N model, followed by optimizing the parameters of the H-N model using the GA. The correlation coefficient of the fitting result can be improved to over 0.98. This study also reveals a close relationship between the optimization of the H-N model and the discreteness and overlap of experimental data, which may be attributed to the inclusion of fractional power functions in the H-N model.