Abstract
OBJECTIVE: To investigate the potential of a hybrid multi-instance learning model (TGMIL) combining Transformer and graph attention networks for classifying gastric adenocarcinoma differentiation on whole-slide images (WSIs) without manual annotation. METHODS AND MATERIALS: A hybrid multi-instance learning model is proposed based on the Transformer and the graph attention network, called TGMIL, to classify the differentiation of gastric adenocarcinoma. A total of 613 WSIs from patients with gastric adenocarcinoma were retrospectively collected from two different hospitals. According to the differentiation of gastric adenocarcinoma, the data were divided into four groups: normal group (n = 254), well differentiation group (n = 166), moderately differentiation group (n = 75), and poorly differentiation group (n = 118). The gold standard of differentiation classification was blindly established by two gastrointestinal pathologists. The WSIs were randomly split into a training dataset consisting of 494 images and a testing dataset consisting of 119 images. Within the training set, the WSI count of the normal, well, moderately, and poorly differential groups was 203, 131, 62, and 98 individuals, respectively. Within the test set, the corresponding WSI count was 51, 35, 13, and 20 individuals. RESULTS: The TGMIL model developed for the differential prediction task exhibited remarkable efficiency when considering sensitivity, specificity, and the area under the curve (AUC) values. We also conducted a comparative analysis to assess the efficiency of five other models, namely MIL, CLAM_SB, CLAM_MB, DSMIL, and TransMIL, in classifying the differentiation of gastric cancer. The TGMIL model achieved a sensitivity of 73.33% and a specificity of 91.11%, with an AUC value of 0.86. CONCLUSIONS: The hybrid multi-instance learning model TGMIL could accurately classify the differentiation of gastric adenocarcinoma using WSI without the need for labor-intensive and time-consuming manual annotations, which will improve the efficiency and objectivity of diagnosis.