Uncovering the lung cancer mechanisms through the chromosome structural ensemble characteristics

Abstract

Lung cancer is one of the most common cancers in human. However, it is still lack of understanding the mechanisms of a normal cell developing to the cancer cell. Here we develop the chromosome dynamic structural model and quantify the important characteristics of the chromosome structural ensemble of the normal lung cell and the lung cancer A549 cell. Our results demonstrate the essential relationship among the chromosome ensemble, the epigenetic marks, and the gene expressions, which suggests the linkage between chromosome structure and function. The analysis reveals that the lung cancer cell may have higher level of relative ensemble fluctuation as well as higher degree of the phase separation between the two compartments than the normal lung cells. In addition, the significant conformational "switching off" events (from compartment A to B) are more than the significant conformational "switching on" events during the lung cancerization. The kinetic lung cancerization pathway is not the same as the reversion pathway by characterizing the hot spots and interaction networks of the lung cancer transitions. These investigations have revealed the cell fate determination mechanism of the lung cancer process, which will be helpful for the further prevention and control of cancers.