Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients

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.

<p>NEDD9 overexpression predicts poor prognosis in solid cancers: a meta-analysis</p>

“…NEDD9 coordinates the focal adhesion kinase and SRC signaling cascades that are involved in integrin-dependent adhesion and migration, invasion, cell apoptosis and life cycle, and survival 2–6. NEDD9 overexpression contributes to solid cancer metastasis in lung, liver, breast, ovarian, colon, glioblastoma carcinoma, and cervical cancers 3,7–13. NEDD9 expression levels are a biomarker of cancer aggression and could be a prognostic factor of solid cancers 14.…”

The Role of Interleukins in Colorectal Cancer

“…Additionally, IL-8 was also found to play a central role in CRC metastasis by inducing the EMT or resistance to anoikis. A protein-protein network analysis demonstrated that IL-8 was one of the four hub genes associated with CRC metastasis [96]. Further investigations showed that IL-8 was significantly higher in patients with stage T3 or T4 CRC, lymph node metastasis or liver metastasis.…”

Multigene panel predicting survival of patients with colon cancer

“…C-index, also known as concordance" statistic or C-statistic, is a measure of goodness of fit for survival outcomes in a CPH model, and higher C-index means higher predictive ability [21]. Therefore, to further confirm the performance of our multigene panel, we compared the C-indexes, calculated by using the R package "survcomp [22]" , with a total of 10 biomarkers reported by others [23][24][25][26][27][28][29][30][31][32][33]. Student T test was used to compare C-indexes between two groups.…”

“…As mentioned above, we compared the performance of our multigene panel with 10 existing biomarkers (including a 4-gene signature [23], a 15-gene signature [24], two 6-gene signatures [25,28], a 10-gene signature [26], a 5-gene signature [27], AEBP1 [29], FZD7 [30], CDX2 [31], MUC2 [31], PPM1H [32], and LAYN [33]). As shown in figure 6, the C-index of our multigene panel was significantly higher or comparable with the existing biomarkers in the training set, test set, TCGA-COAD, and GSE17536, indicating that our multigene panel had comparable prognostication performance.…”