Kinase-substrate Edge Biomarkers Provide a More Accurate Prognostic Prediction in ER-negative Breast Cancer

The estrogen receptor(ER)-negative breast cancer subtype is aggressive with few treatment options available.To identify specific prognostic factors for ER-negative breast cancer,this study included 705,729 and 1034 breast invasive cancer patients from the Surveillance,Epidemiology,and End Results(SEER)and The Cancer Genome Atlas(TCGA)databases,respectively.To identify key differential kinase-substrate node and edge biomarkers between ER-negative and ERpositive breast cancer patients,we adopted a network-based method using correlation coefficients between molecular pairs in the kinase regulatory network.Integrated analysis of the clinical and molecular data revealed the significant prognostic power of kinase-substrate node and edge features for both subtypes of breast cancer.Two promising kinase-substrate edge features,CSNK1A1-NFATC3 and SRC-OCLN,were identified for more accurate prognostic prediction in ERnegative breast cancer patients.

Computational prediction and functional analysis of arsenic-binding proteins in human cells

Background:Arsenic has a broad anti-cancer ability against hematologic malignancies and solid tumors.To systematically understand the biological functions of arsenic,we need to identify arsenic-binding proteins in human cells.However,due to lack of effective theoretical tools and experimental methods,only a few arsenic-binding proteins have been identified.Methods:Based on the crystal structure of ArsM,we generated a single mutation free energy profile for arsenic binding using free energy perturbation methods.Multiple validations provide an indication that our computational model has the ability to predict arsenic-binding proteins with desirable accuracy.We subsequently apply this computational model to scan the entire human genome to identify all the potential arsenic-binding proteins.Results:The computationally predicted arsenic-binding proteins show a wide range of biological functions,especially in the signaling transduction pathways.In the signaling transduction pathways,arsenic directly binds to the key factors(e.g.,Notch receptors,Notch ligands,Wnt family proteins,TGF-beta,and their interacting proteins)and results in significant inhibitions on their enzymatic activities,further having a crucial impact on the related signaling pathways.Conclusions:Arsenic has a significant impact on signaling transduction in cells.Arsenic binding to proteins can lead to dysfunctions of the target proteins,having crucial impacts on both signaling pathway and gene transcription.We hope that the computationally predicted arsenic-binding proteins and the functional analysis can provide a novel insight into the biological functions of arsenic,revealing a mechanism for the broad anti-cancer of arsenic.