Computational Image Analysis Identifies Histopathological Image Features Associated With Somatic Mutations and Patient Survival in Gastric Adenocarcinoma

Computational analysis of histopathological images can identify sub-visual objective image features that may not be visually distinguishable by human eyes, and hence provides better modeling of disease phenotypes. This study aims to investigate whether specific image features are associated with somatic mutations and patient survival in gastric adenocarcinoma (sample size = 310). An automated image analysis pipeline was developed to extract quantitative morphological features from H&E stained whole-slide images. We found that four frequently somatically mutated genes (TP53, ARID1A, OBSCN, and PIK3CA) were significantly associated with tumor morphological changes. A prognostic model built on the image features significantly stratified patients into low-risk and high-risk groups (log-rank test p-value = 2.6e-4). Multivariable Cox regression showed the model predicted risk index was an additional prognostic factor besides tumor grade and stage. Gene ontology enrichment analysis showed that the genes whose expressions mostly correlated with the contributing features in the prognostic model were enriched on biological processes such as cell cycle and muscle contraction. These results demonstrate that histopathological image features can reflect underlying somatic mutations and identify high-risk patients that may benefit from more precise treatment regimens. Both the image features and pipeline are highly interpretable to enable translational applications.