Abstract
ObjectiveThe mechanism underlying colon cancer metastasis remain unclear. This study aimed to elucidate the genes alteration during the metastasis of colon cancer and identify genes that crucial to the metastasis and survival of colon cancer patients.MethodsThe dataset of primary and metastasis tissue of colon cancer, and dataset of high and low metastasis capability of colon cancer cells were selected as training cohort, and the overlapped differentially expressed genes (DEGs) were screened from the training cohort. The functional enrichment analysis for the overlapped DEGs was performed. The prognostic value of overlapped DEGs were analyzed in The Cancer Genome Atlas dataset, and a gene signature was developed using genes that related to the overall survival (OS). The prognostic value of the gene signature was further confirmed in a validation cohort.ResultsA total of 184 overlapped DEGs were screened from the training cohort. Functional enrichment analysis revealed the significant gene functions and pathways of the overlapped DEGs. Four hub genes (3-oxoacid CoA-transferase 1, actinin alpha 4, interleukin 8, integrin subunit alpha 3) were identified using protein–protein network analysis. Six genes (aldehyde dehydrogenase 2, neural precursor cell expressed, developmentally down-regulated 9, filamin A, lamin B receptor, twinfilin actin binding protein 1, serine and arginine rich splicing factor 1) were closely related to the OS of colon cancer patients. A gene signature was developed using these six genes based on their risk score, and the validation cohort indicated that the prognostic value of this gene signature was high in the prediction of colon cancer patients.ConclusionsOur study demonstrates a gene profiles related to the metastasis of colon cancer, and identify a six-gene signature that acts as an independent biomarker on the prognosis of colon cancer.
Highlights
Colorectal cancer (CRC) is one of the leading malignant cancers in the world, and colon cancer accounts for a large part of CRC (Siegel et al, 2017; Siegel, Miller & Jemal, 2017)
A total of 341 differentially expressed genes (DEGs) between colon cancer cells lines SW420 and SW680 cells were identified in GSE2509 dataset, and 7339 DEGs between primary and metastasis tumor specimens were identified in the GSE40367 dataset
Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis The gene functions of the 184 overlapped DEGs were analyzed by GO and KEGG enrichment analysis
Summary
Colorectal cancer (CRC) is one of the leading malignant cancers in the world, and colon cancer accounts for a large part of CRC (Siegel et al, 2017; Siegel, Miller & Jemal, 2017). Cancer metastasis remains one of the main causes of death in these patients. One studied showed that the prognosis of patients with distant metastasis remained poor compared to the prognosis of patients with early-stage colon cancer (Siegel, Miller & Jemal, 2017). Accumulation of genetic mutations is recognized as one of the important causes for the pathogenesis and progression of colon cancer (Sameer, 2013). Exploring the mechanisms of cancer metastasis and searching suitable predictors are crucial to the diagnosis and treatment of colon cancer
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