Novel digital signatures of tissue phenotypes for predicting distant metastasis in colorectal cancer

Abstract

Distant metastasis is the major cause of death in colorectal cancer (CRC). Patients at high risk of developing distant metastasis could benefit from appropriate adjuvant and follow-up treatments if stratified accurately at an early stage of the disease. Studies have increasingly recognized the role of diverse cellular components within the tumor microenvironment in the development and progression of CRC tumors. In this paper, we show that automated analysis of digitized images from locally advanced colorectal cancer tissue slides can provide estimate of risk of distant metastasis on the basis of novel tissue phenotypic signatures of the tumor microenvironment. Specifically, we determine what cell types are found in the vicinity of other cell types, and in what numbers, rather than concentrating exclusively on the cancerous cells. We then extract novel tissue phenotypic signatures using statistical measurements about tissue composition. Such signatures can underpin clinical decisions about the advisability of various types of adjuvant therapy.