Systems Biology (Methods in Molecular Biology)

that the relative content or activity assumptions will not affect

validation, because many experimental data such as gene expression

level is also relative. Other molecular-cellular agents in the endoge-

nous molecular-cellular network of liver are quantified in a similar

way, the endogenous molecular-cellular network of liver was trans-

formed into a set of ordinary differential equations which implies

some attractors underlying the molecular-cellular network of

liver [49].

2.4 Normal Liver
and HCC Are Stable
States of Endogenous
Network

According to the ordinary differential equations, we obtain five

attractors that may have obvious or non-obvious biological func-

tions in Table1. Each attractor is specified by the relative content or

activity of these molecular-cellular agents. According to the expres-

sion or the activation level of these agents we can judge the status,

ON or OFF, of the functional modules in each attractor. ON means

the expressional or activation level of the molecular-cellular agents

supports the execution of the functional module, while OFF means

the expression of activation of these agents did not support the

execution of the functional module. In Table1, we summarize the

status of these functional modules, including cell cycle, metabo-

lism, liver-specific function, cell death, cell adhesion, immune

response, and angiogenesis, in each attractor. On the other hand,

we also summarize the status of these functional modules in normal

liver and HCC form clinical and experimental data in Table 1

[45]. Two attractors obtained from the model have a perfect

match with normal liver and HCC respectively when comparing

model results with clinical and experimental results. So, we prelim-

inarily conclude that the two attractors of the model reproduce the

clinical normal liver and HCC.

Table 1
Model result and clinical observations at the modular level

Model results Clinical observation [45]

A B C D Normal hepatocyte Cancerous hepatocyte

Cell cycle OFF ON OFF ON OFF ON

Liver differentiation ON OFF ON OFF ON OFF

Apoptosis OFF OFF ON OFF OFF OFF

Cell adhesion ON OFF OFF OFF ON OFF

Proliferative metabolism OFF ON OFF ON OFF ON

Immune response OFF ON ON OFF OFF ON

Angiogenesis OFF ON OFF ON OFF ON

Stable states A and B reproduced the key features of normal hepatocyte and cancerous hepatocyte at the modular level

224 Gaowei Wang et al.