Two-stage Cox-nnet: biologically interpretable neural-network model for prognosis prediction and its application in liver cancer survival using histopathology and transcriptomic data

作者：Zhucheng Zhan, Zheng Jing, Bing He, Noshad Hosseini, Maria Westerhoff, Eun-Young Choi, Lana X. Garmire · 发表于：NAR Genomics and Bioinformatics · 年份：2021 · DOI：10.1093/nargab/lqab015 · 被引用次数：30 · 研究领域：AI in cancer detection、Cell Image Analysis Techniques、Radiomics and Machine Learning in Medical Imaging

Abstract Pathological images are easily accessible data with the potential of prognostic biomarkers. Moreover, integration of heterogeneous data types from multi-modality, such as pathological image and gene expression data, is invaluable to help predicting cancer patient survival. However, the analytical challenges are significant. Here, we take the hepatocellular carcinoma (HCC) pathological image features extracted by CellProfiler, and apply them as the input for Cox-nnet, a neural network-based prognosis prediction model. We compare this model with the conventional Cox proportional hazards (Cox-PH) model, CoxBoost, Random Survival Forests and DeepSurv, using C-index and log-rank P-values. The results show that Cox-nnet is significantly more accurate than Cox-PH and Random Survival Forests models and comparable with CoxBoost and DeepSurv models, on pathological image features. Further, to integrate pathological image and gene expression data of the same patients, we innovatively construct a two-stage Cox-nnet model, and compare it with another complex neural-network model called PAGE-Net. The two-stage Cox-nnet complex model combining histopathology image and transcriptomic RNA-seq data achieves much better prognosis prediction, with a median C-index of 0.75 and log-rank P-value of 6e−7 in the testing datasets, compared to PAGE-Net (median C-index of 0.68 and log-rank P-value of 0.03). Imaging features present additional predictive information to gene expression features, ...