Overall mortality risk analysis for rectal cancer using deep learning-based fuzzy systems

Colorectal cancer is a leading cause of cancer mortality worldwide, with an increasing incidence rate in developing countries. Integration of genetic information with cancer therapy guidance has shown promise in cancer treatment, indicating its potential as an essential tool in translation oncology. However, the high-throughput analysis and variability of genomic data poses a major challenge to conventional analytic approaches. In this study, we propose an advanced analytic approach, named "Fuzzy-based RNNCoxPH," incorporated fuzzy logic, recurrent neural networks (RNNs), and Cox proportional hazards regression (CoxPH) for detecting missense variants associated with high-risk of all-cause mortality in rectum adenocarcinoma. The test data set was downloaded from "Rectum adenocarcinoma, TCGA-READ" the Genomic Data Commons (GDC) portal. In this study, four model-based risk score models were derived using RNN, CoxPH, RNNCoxPHAddition, and RNNCoxPHMultiplication. The RNNCoxPHAddition and RNNCoxPHMultiplication models were obtained as the sum and product of the RNN risk degree matrix and the CoxPH risk degree matrix, respectively. Moreover, the fuzzy logic system was used to calculate the survival risk values of missense variants and classified their membership grade to improve the identification of high-risk gene variation locations associated with cancer mortality. The four models were integrated to develop an advanced risk estimation model. There were 20 028 variants associated with survival status, amongst 17 638 variants were associated with survival and 2390 variants associated with mortality. The proposed Fuzzy-based RNNCoxPH model obtained a balanced accuracy of 93.7%, which was significantly higher than that of the other four test methods. In particular, the CoxPH model is commonly used in medical researches and the XGBoost model is famous for its high accuracy in machine learning. The results suggest that the Fuzzy-based RNNCoxPH model exhibits a higher efficacy in identifying and classifying the missense variants related to mortality risk in rectum adenocarcinoma.