Investigating the Biological Determinants of Early Lung Adenocarcinoma Behavior Through Data Integration

Abstract

Lung adenocarcinoma (LUAD) is a heterogeneous group of tumors associated with different survival rates, even when detected at an early stage. While screening programs have proven to significantly increase the chance of survival in high-risk individuals, there is also a high probability of overdiagnosis. Therefore, the molecular determinants of early tumor development behavior need to be further investigated. Furthermore, as LUAD is a consequence of complex biological processes, it is necessary to take an integrative approach combining data from different modalities to understand the interrelationships of multiple biological layers and their functions. Here, I aim to investigate the biological determinants of early LUAD indolence or aggressiveness. I hypothesize that the integration of biological, clinical and radiomics data of early stage LUAD will improve the discrimination between indolent and aggressive tumors which in turn may offer novel and personalized avenues for intervention. The main findings show insightful biological differences between these groups of patients, which include increased immune response for indolent tumors, increased proliferation signaling for aggressive tumors, and highly active stromal modification signaling for both, indolent being more mesenchymal-like and aggressive more fibrogenic and collagen heavy. Some of these signatures were associated with specific radiomics features. This dissertation provides a comprehensive and deep profiling of LUAD indolence and aggressiveness at the biological bulk and single cell levels, as well as at the clinical and radiomics levels. It also highlights the importance and power of data integration to improve our systemic understanding of LUAD and to help reduce the gap between basic science research and clinical practice.