Identification of Hub Genes Related to Liver Metastasis of Colorectal Cancer by Integrative Analysis

Abstract

Liver metastasis of colorectal cancer (LMCRC) severely damages patient health, causing poor prognosis and tumor relapse. Marker genes associated with LMCRC identified by previous study did not meet therapeutic demand. Therefore, it is necessary to identify new biomarkers regulating the metastasis network and screen potential drugs for future treatment. Here, we identified that cell adhesion molecules and peroxisome proliferator-activated receptor (PPAR) signaling pathway were significantly enriched by analyzing the integrated-multiple expression profiles. Moreover, analysis with robust rank aggregation approach revealed a total of 138 differentially expressed genes (DEGs), including 108 upexpressed and 30 downexpressed genes. With establishing protein–protein interaction network, we also identified the subnetwork significantly enriching the metastasis-associated hub genes including ALB, APOE, CDH2, and ORM1. ESR2, FOXO3, and SRY were determined as key transcription factors regulating hub genes. In addition, ADH-1, epigallocatechin, CHEMBL1945287, and cochinchinenin C were predicted as potential therapeutic drugs. Moreover, the antimigration capacity of ADH-1 and epigallocatechin were confirmed in CRC cell lines. In conclusion, our findings not only offer opportunities to understand metastasis mechanism but also identify potential therapeutic targets for CRC.

Integrated analysis identifies cuproptosis-related gene DLAT and its competing endogenous RNAs network to predict the prognosis of pancreatic adenocarcinoma patients

“…Bioinformatics analysis was performed according to a previous study. [ 36 ] Additionally, a CRGs prognostic signature was constructed in PAAD patients from the TCGA cohort and validated in 2 GEO datasets. The molecular characteristics and functions of different CRGs subgroups were also investigated.…”

Hepatic passaging of NRAS-mutant melanoma influences adhesive properties and metastatic pattern

“…One of the most-upregulated genes was Capg (gelsolin-like actin-capping protein) which was identified as poor prognostic factor for various cancers, especially liver metastasis of CRC [ 56 , 57 ]. Moreover, Apoe (Apolipoprotein E) was upregulated which is a hub gene for liver metastasis of CRC and a negative predictive factor [ 58 , 59 ]. On the contrary, strongly downregulated genes included Igfbp3 (insulin like growth factor binding protein 3) that led to downstream activation of AKT.…”

Comprehensive Analysis of Potential Prognostic Values of ANGPTLs in Colorectal Cancer

“…The addition of bevacizumab could only increase the median overall survival time by approximately 1 to 5 months [ 45 , 46 ]. Although our previous study had performed an integrated analysis, which identified the potential hub genes serving as therapeutic targets and screened novel drugs in preventing CRC liver metastasis [ 47 ], the clinical practice is still limited. Therefore, it is necessary to further clarify the exact mechanisms of CRC metastasis and explore some novel molecules that might be applied for CRC targeted therapy.…”