Surrogate Biomarker Prediction from Whole-Slide Images for Evaluating Overall Survival in Lung Adenocarcinoma

Recent advances in computational pathology have shown potential in predicting biomarkers from haematoxylin and eosin (H&E) whole-slide images (WSI). However, predicting the outcome directly from WSIs remains a substantial challenge. In this study, we aimed to investigate how gene expression, predicted from WSIs, could be used to evaluate overall survival (OS) in patients with lung adenocarcinoma (LUAD).

Differentially expressed genes (DEGs) were identified from The Cancer Genome Atlas (TCGA)-LUAD cohort. Cox regression analysis was performed on DEGs to identify the gene prognostics of OS. Attention-based multiple instance learning (AMIL) models were trained to predict the expression of identified prognostic genes from WSIs using the TCGA-LUAD dataset. Models were externally validated in the Clinical Proteomic Tumour Analysis Consortium (CPTAC)-LUAD dataset. The prognostic value of predicted gene expression values was then compared to the true gene expression measurements.

The expression of 239 prognostic genes could be predicted in TCGA-LUAD with cross-validated Pearson's R > 0.4. Predicted gene expression demonstrated prognostic performance, attaining a cross-validated concordance index of up to 0.615 in TCGA-LUAD through Cox regression. In total, 36 genes had predicted expression in the external validation cohort that was prognostic of OS.

Gene expression predicted from WSIs is an effective method of evaluating OS in patients with LUAD. These results may open up new avenues of cost- and time-efficient prognosis assessment in LUAD treatment.