Systems biomedicine of primary and metastatic colorectal cancer reveals potential therapeutic targets

Abstract

Colorectal cancer (CRC) is one of the major causes of cancer deaths across the world. Patients survival time at time of diagnosis depends largely on stage of the tumor. Therefore, understanding the molecular mechanisms promoting cancer progression from early stages to high-grade stages is essential for implementing therapeutic approaches. To this end, we performed a unique meta-analysis flowchart by identifying differentially expressed genes (DEGs) between normal, primary and metastatic samples in some test datasets. DEGs were employed to construct a protein-protein interaction (PPI) network. Then, a smaller network containing 39 DEGs were extracted from the PPI network whose nodes expression induction or suppression alone or in combination with each other would inhibit tumor progression or metastasis. A number of these DEGs were then verified by gene expression profiling, survival analysis and a number of validation datasets from different genomic repositories. They were involved in cell proliferation, energy production under hypoxic conditions, epithelial to mesenchymal transition (EMT) and angiogenesis. Multiple combination targeting of these DEGs were proposed to have high potential in preventing cancer progression. Some genes were also presented as diagnostic biomarkers for colorectal cancer. Finally, TMEM131, DARS and SORD genes were identified in this study which had never been associated with any kind of cancer neither as a biomarker nor curative target.