Identification of novel biomarkers affecting the metastasis of colorectal cancer through bioinformatics analysis and validation through qRT-PCR

Abstract

Background: Tumor progression and distant metastasis are the main causes of deaths in colorectal cancer (CRC) patients, and the molecular mechanisms in CRC metastasis have not been completely discovered. Methods: We identified differentially expressed genes (DEGs) and lncRNAs (DELs) of CRC from The Cancer Genome Atlas (TCGA) database. Then we conducted the weighted gene co-expression network analysis (WGCNA) to investigate co-expression modules related with CRC metastasis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, DEG-DEL co-expression network and survival analyses of significant modules were also conducted. Finally, the expressions of selected biomarkers were validated in cell lines by quantitative real-time PCR (qRT-PCR). Results: 2032 DEGs and 487 DELs were involved the construction of WGCNA network, and greenyellow, turquoise and brown module were identified to have more significant correlation with CRC metastasis. GO and KEGG pathway analysis of these three modules have proven that the functions of DEGs were closely involved in many important processes in cancer pathogenesis. Through the DEG-DEL co-expression network, 12 DEGs and 2 DELs were considered as hub nodes. Besides, survival analysis showed that 30 DEGs were associated with the overall survival of CRC. Then 10 candidate biomarkers were chosen for validation and the expression of CA2, CHP2, SULT1B1, MOGAT2 and C1orf115 were significantly decreased in CRC cell lines when compared to normal human colonic epithelial cells, which were consistent with the results of differential expression analysis. Especially, low expression of SULT1B1, MOGAT2 and C1orf115 were closely correlated with poorer survival of CRC. Conclusion: This study identified 5 genes as new biomarkers affecting the metastasis of CRC. Besides, SULT1B1, MOGAT2 and C1orf115 might be implicated in the prognosis of CRC patients.

A Novel Metabolism-Related Signature as a Candidate Prognostic Biomarker for Hepatocellular Carcinoma

“… 31 , 32 Lian et al reported that MOGAT2 could have applications as a novel biomarker affecting the metastasis of colorectal cancer treatment. 33 So far, little is known about the existence of molecular links between MOGAT2 and HCC. In our study, however, MOGAT2 was found to be highly decreased which might indicate its protective role as a prognostic marker in HCC.…”

Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice

“…CRC developed through a multistep process from normal epithelium to adenoma and adenocarcinoma, which can eventually metastasize to different organs [ 5 ]; it was shown that the transition of CRC cells from early stages to late stages (metastasis) is associated with a significant change in the cellular gene expression profile [ 6 ]. These genetic alterations have led to the emergence of the novel strategies for personalized medicine programs [ 7 , 8 ]. Moreover, the correlation between colorectal inflammation and increased colitis-associated tumorigenesis has been identified in some epidemiological and clinical studies [ 9 , 10 ], which is characterized by high mortality and is closely associated with inflammatory bowel disease [ 11 ].…”

A Prognostic Model Using Immune-Related Genes for Colorectal Cancer

“…Many CRC models have reported that CHP2, GNAI1, and RETNLB are important to core pathway genes in the progression of CRC. Several genes were identified as biomarkers affecting CRC metastasis, including ChP2, and their low expression in CRC cell lines was confirmed, compared with normal colorectal epithelial cell lines (Liang et al, 2016;Lian et al, 2020;Ma et al, 2020). SPP1 levels were found to be increased in the blood of CRC patients, and their expression was related to a poor prognosis.…”