Abstract
BackgroundColorectal cancer (CRC), one of the most common malignant tumors worldwide, has a high mortality rate, especially for patients with CRC liver metastasis (CLM). However, CLM pathogenesis remains unclear.MethodsWe integrated multiple cohort datasets and databases to clarify and verify potential key candidate biomarkers and signal transduction pathways in CLM. GEO2R, DAVID 6.8, ImageGP, STRING, UALCAN, ONCOMINE, THE HUMAN PROTEIN ATLAS, GEPIA 2.0, cBioPortal, TIMER 2.0, DRUGSURV, CRN, GSEA 4.0.3, FUNRICH 3.1.3 and R 4.0.3 were utilized in this study.ResultsSixty-three pairs of matched colorectal primary cancer and liver metastatic gene expression profiles were screened from three gene expression profiles (GSE6988, GSE14297 and GSE81558). Thirty-one up-regulated genes and four down-regulated genes were identified from these three gene expression profiles and verified by another gene expression profiles (GSE 49355) and TCGA database. Two pathways (IGFBP-IGF signaling pathway and complement-coagulation cascade), eighteen key differentially expressed genes (DEGs), six hub genes (SPARCL1, CDH2, CP, HP, TF and SERPINA5) and two biomarkers (CDH2 and SPARCL1) with significantly prognostic values were screened by multi-omics data analysis and verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohort.ConclusionsIn this study, we identified a robust set of potential candidate biomarkers in CLM, which would provide potential value for early diagnosis and prognosis, and would promote molecular targeting therapy for CRC and CLM.
Highlights
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide
Genomic features of this dataset of liver metastases from CRC patients with expression arrays include a total of 51 samples, including 23 primary CRCs, 19 liver metastases, and nine normal colon mucosal tissues; from this, we selected sample data from 19 pairs of CRC primary cancer and liver metastasis tissues
We found that these Differentially Expressed Genes (DEG) play a role in the following pathways: chemical carcinogenesis, metabolism of xenobiotics via cytochrome P450, linoleic acid metabolism, insulin-like growth factor binding proteins (IGFBPs) that regulate the transport and uptake of insulin-like growth factors (IGFs), post-translational protein phosphorylation, platelet degranulation, activation, aggregation, and other signaling pathways
Summary
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Colorectal cancer liver metastasis (CLM) is one of the primary causes of this high mortality rate, which occurs in 30% of CRC patients, accounting for two-thirds of the related deaths [2]. The occurrence and development of CLM involves a myriad of epigenetic and genetic changes within multiple functional signaling pathways. These different networks are susceptible to regulation by genetic and epigenetic events, leading to diversity in the expression profiles. Colorectal cancer (CRC), one of the most common malignant tumors worldwide, has a high mortality rate, especially for patients with CRC liver metastasis (CLM).
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