Performance of Machine Learning in Diagnosing KRAS (Kirsten Rat Sarcoma) Mutations in Colorectal Cancer: Systematic Review and Meta-Analysis

Abstract Background With the widespread application of machine learning (ML) in the diagnosis and treatment of colorectal cancer (CRC), some studies have investigated the use of ML techniques for the diagnosis of KRAS (Kirsten rat sarcoma) mutation. Nevertheless, there is scarce evidence from evidence-based medicine to substantiate its efficacy. Objective Our study was carried out to systematically review the performance of ML models developed using different modeling approaches, in diagnosing KRAS mutations in CRC. We aim to offer evidence-based foundations for the development and enhancement of future intelligent diagnostic tools. Methods PubMed, Cochrane Library, Embase, and Web of Science were systematically retrieved, with the search cutoff date set to December 22, 2024. The encompassed studies are publicly published research papers that use ML to diagnose KRAS gene mutations in CRC. The risk of bias in the encompassed models was evaluated via the PROBAST (Prediction Model Risk of Bias Assessment Tool). A meta-analysis of the model’s concordance index (c-index) was performed, and a bivariate mixed-effects model was used to summarize sensitivity and specificity based on diagnostic contingency tables. Results A total of 43 studies involving 10,888 patients were included. The modeling variables were derived from clinical characteristics, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography/computed tomography, and pathological histology. In the validation cohort, for the ML model developed based on CT radiomic features, the c-index, sensitivity, and specificity were 0.87 (95% CI 0.84‐0.90), 0.85 (95% CI 0.80‐0.89), and 0.83 (95% CI 0.73‐0.89), respectively. For the model developed using MRI radiomic features, the c-index, sensitivity, and specificity were 0.77 (95% CI 0.71‐0.83), 0.78 (95% CI 0.72‐0.83), and 0.73 (95% CI 0.63‐0.81), respectively. For the ML model developed based on positron emission tomography/computed tomography radiomic features, the c-index, sensitivity, and specificity were 0.84 (95% CI 0.77‐0.90), 0.73, and 0.83, respectively. Notably, the deep learning (DL) model based on pathological images demonstrated a c-index, sensitivity, and specificity of 0.96 (95% CI 0.94‐0.98), 0.83 (95% CI 0.72‐0.91), and 0.87 (95% CI 0.77‐0.92), respectively. The DL model MRI-based model showed a c-index of 0.93 (95% CI 0.90‐0.96), sensitivity of 0.85 (95% CI 0.75‐0.91), and specificity of 0.83 (95% CI 0.77‐0.88). Conclusions ML is highly accurate in diagnosing KRAS mutations in CRC, and DL models based on MRI and pathological images exhibit particularly strong diagnosis accuracy. More broadly applicable DL-based diagnostic tools may be developed in the future. However, the clinical application of DL models remains relatively limited at present. Therefore, future research should focus on increasing sample sizes, improving model architectures, and developing more advanced DL models to facilitate the creation of highly efficient intelligent diagnostic tools for KRAS mutation diagnosis in CRC.