Morphological basis of the lung adenocarcinoma subtypes: CompuCell3D models and code.

Abstract

This repository contains source code for the the CompuCell3D models as well as explanatory text, data and results for Lung adenocarcinoma (LUAD).

Lung adenocarcinoma (LUAD), which accounts for a large proportion of lung cancers, is divided into five major subtypes based on histologic characteristics. The clinical characteristics, prognosis, and responses to treatments vary among subtypes. Here, we demonstrate the variations of cell-cell contact energy result in the LUAD subtype-specific morphogenesis. We reproduced the morphologies of the papillary LUAD subtypes with the Cellular Potts Model (CPM). Simulations and experimental validations revealed modifications of cell-cell contact energy changed the morphology from a papillary-like structure to micropapillary or solid subtype-like structures. Remarkably, differential gene expression analysis revealed subtype-specific expressions of genes relating to cell adhesion that changes cell-cell contact energy, and most subtype-specific cell adhesion genes correlated with patient prognosis. Knock-down experiments of the micropapillary-specific ITGA11 gene resulted in the morphological changes of the spheroids produced from a LUAD cell line PC9.