1) The document describes a Markov Chain model built to predict gene expression signatures associated with epithelial and mesenchymal cells based on data from 1165 breast cancer patients. 2) The model incorporates the known TGFB-induced EMT pathway and regulatory relationships between molecules to recursively predict expression likelihood. 3) Expression patterns are mapped to epithelial and mesenchymal cell types based on the expression level of the CDH1 gene, which plays a key role in cell phenotype and the initiation of EMT.

1. Prediction of Gene Signatures in TGFB-induced
Breast Cancer Metastasis by Markov Chain Model
Yang Cong, Shenyi Chen, Stephen T.C. Wong
Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, 6670 Berter Ave, Houston, TX 77030
Abstract
Introduction
TGFB-EMT pathway
CDH1 transcription factor selection
Expression Signature Prediction
Results
Acknowledgements
•NCI Center for Modeling Cancer Development U54 Ca149196
Metastasis is a major cause of patient death in breast cancer.
Epithelial-mesenchymal transition (EMT) plays the initiation
role in the metastasis cascade. Based on gene profiling data
of 1165 breast cancer patients in TCGA, we built a statistical
Markov Chain model to predict gene signatures of epithelial
and mesenchymal cells. Based on the literature integrated
TGFB-induced EMT pathway, we extracted the regulatory
mechanism among molecules. We used a recursive
algorithm to predict the likelihood of expression signatures
and further mapped the prediction with known epithelial
and mesenchymal expression patterns.
A molecule is regulated by its regulators, and the change of its
expression level only depends on the observed expression of
all its regulators
The loss of the epithelial adhesion molecule E-cadherin
(CDH1) is considered as a fundamental event in EMT and an
early step in cancer metastasis. EMT can be induced by
several growth factors, such as TGFB1, hepatocyte growth
factor, and platelet-derived growth factor PDGF. Also EMT
can be induced by any one of the following transcription
factors alone, such as SNAI1, SNAI2, TWIST1, FOXC1, FOXC2,
ZEB1 and ZEB2.
A central target of these transcription factors listed above is
the repression of E-cadherin gene CDH1. The expression level
of CDH1 plays a key role in the cell phenotype. The inhibition
of CDH1 expression is the starter of EMT process. Epithelial
cells have a high expression level of CDH1, meanwhile
mesenchymal cells have a low expression. Hence, we map the
expression patterns with cell types based on the expression
level of CDH1.
Data Processing