Colorectal Cancer Heterogeneity As Robust Intrinsic States Formed By A Molecular Interaction Network

Colorectal cancer(CRC)as a heterogeneous disease shows different response with treatment and variable prognosis.Therefore,it is necessary to classify CRC so that every subtype can be treated in a particular method.Biostatistics analysis of expression data is the primary CRC classification strategy currently.However,this strategy relies on data features and analytical methods seriously,which cannot reveal general rules.Otherwise,this article indicates statistical analysis can fail to reveal underlying true biological mechanism for the universal stochastics effect in biological progress.In pursuing a mechanistic understanding behind such complexity,we constructed a core molecular–cellular interaction network underlying CRC and investigated its nonlinear dynamical properties.The network dynamics reveal a landscape of several attractive basins corresponding to both normal intestinal phenotype and robust tumors subtypes,identified by their different molecular signatures.Comparison between the modelling results and gene expression profiles from patients collected at the second affiliated hospital of Zhejiang University is presented as validation.Combining theory prediction and experiment data,we suggest that CRC pathogenesis may depend on pathways involved in gastrointestinal track development and molecules associated with mesenchymal lineage differentiation,such as Stat5,BMP,Runx and Hox transcription families.