Co-expression Network Analysis Identified Key Proteins in Association With Hepatic Metastatic Colorectal Cancer

Abstract

Purpose: Intense efforts have been made in colorectal cancer (CRC) treatment in recent decades. However, the mechanism of development and metastasis of CRC has not been fully cleared. This study is designed to identify key proteins involved in stage III and hepatic metastatic CRC.

Experiment design: Protein expression profiles of paired tumor and benign tissue samples from stage III and hepatic metastatic CRC patients are characterized by using a label-free proteomics approach. Key proteins relevant to hepatic metastatic CRC are revealed by weighted gene correlation network analysis (WGCNA) and other bioinformatics tools.

Results: WGCNA reveals three hub modules: CRC without specific stage (turquoise), stage III CRC (blue), and hepatic metastatic CRC (green). Nine key proteins (heat shock protein family D member 1 (HSPD1), eukaryotic translation elongation factor 1 gamma, heterogeneous nuclear ribonucleoprotein A2/B1, fibrinogen beta chain (FGB), Talin 1, adaptor related protein complex 2 subunit alpha 2, serrate RNA effector molecule homolog, apolipoprotein C3, phosphoglucomutase 5) are identified. Moreover, upregulation of HSPD1 is validated in CRC tissue by the immunohistochemistry. Upregulation of fibrinogen is validated in metastatic CRC by plasma fibrinogen assay.

Conclusion and clinical relevance: This study provides the proteomic analysis of stage III and hepatic metastatic CRC to identify key proteins of CRC. FGB plays a key role to serve as diagnostic and therapeutic biomarkers for hepatic metastatic CRC.

Keywords: colorectal cancer; fibrinogen beta chain (FGB); hepatic metastasis; label free proteomics; weighted correlation network analysis (WGCNA).