Explainable cancer factors discovery: Shapley additive explanation for machine learning models demonstrates the best practices in the case of pancreatic cancer

Pancreatic cancer is one of digestive tract cancers with high mortality rate. Despite the wide range of available treatments and improvements in surgery, chemotherapy, and radiation therapy, the five-year prognosis for individuals diagnosed pancreatic cancer remains poor. There is still research to be done to see if immunotherapy may be used to treat pancreatic cancer. The goals of our research were to comprehend the tumor microenvironment of pancreatic cancer, found a useful biomarker to assess the prognosis of patients, and investigated its biological relevance. In this paper, machine learning methods such as random forest were fused with weighted gene co-expression networks for screening hub immune-related genes (hub-IRGs). LASSO regression model was used to further work. Thus, we got eight hub-IRGs. Based on hub-IRGs, we created a prognosis risk prediction model for PAAD that can stratify accurately and produce a prognostic risk score (IRG_Score) for each patient. In the raw data set and the validation data set, the five-year area under the curve (AUC) for this model was 0.9 and 0.7, respectively. And shapley additive explanation (SHAP) portrayed the importance of prognostic risk prediction influencing factors from a machine learning perspective to obtain the most influential certain gene (or clinical factor). The five most important factors were TRIM67, CORT, PSPN, SCAMP5, RFXAP, all of which are genes. In summary, the eight hub-IRGs had accurate risk prediction performance and biological significance, which was validated in other cancers. The result of SHAP helped to understand the molecular mechanism of pancreatic cancer.