Interpretable Machine Learning Models Based on Blood Cell-Derived Inflammatory Indices for Identifying Colorectal...

Noninvasive approaches for the risk assessment of colorectal neoplasia remain limited, particularly in terms of interpretability and clinical applicability. This study aimed to develop and validate interpretable machine learning models using blood cell-derived inflammatory indices to identify colorectal adenoma (CRA) and colorectal cancer (CRC).

This retrospective study included 1301 participants from the Second Affiliated Hospital of Guangxi Medical University between January 2017 and April 2022, comprising 487 healthy controls (HC), 327 patients with CRA, and 487 patients with CRC. Restricted cubic spline (RCS) analysis was performed to evaluate the associations between inflammatory indices and colorectal neoplasia. Least absolute shrinkage and selection operator regression and the Boruta algorithm were used for feature selection. Five machine learning algorithms were applied and compared: logistic regression, support vector machine, k-nearest neighbors, random forest, and extreme gradient boosting (XGB). Model performance was evaluated using receiver operating characteristic analysis, calibration curves, and decision curve analysis. SHapley Additive exPlanations (SHAP) was applied to enhance interpretability.

Eight blood cell-derived inflammatory indices differed significantly across groups and showed stage-related alterations. RCS analysis revealed dose-response relationships between inflammatory indices and colorectal neoplasia. Among the five algorithms, XGB achieved the best performance in the validation cohort, with areas under the curve of 0.928 (95% CI, 0.900-0.957) for CRC and 0.829 (95% CI, 0.777-0.880) for CRA. The models also showed good calibration and favorable clinical net benefit. SHAP analysis identified the platelet-to-lymphocyte ratio (PLR) as an important shared predictor, whereas the platelet-to-neutrophil ratio (PNR) and aggregate index of systemic inflammation (AISI) contributed more prominently to the prediction of CRC and CRA, respectively.

XGB models incorporating blood cell-derived inflammatory indices demonstrated promising discriminatory ability and interpretability, and may serve as a noninvasive adjunct for colorectal neoplasia risk stratification pending further validation in prospective and external cohorts.