Abstract
Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosis-related genes associated with distant metastasis and develop therapeutic strategies for COAD patients.Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA; n = 514) cohort were analyzed as a discovery dataset. Next, the data from the GEPIA database and PROGgeneV2 database were used to validate our analysis. Key genes were identified based on the differential miRNA and mRNA expression with respect to M stage. The potential drugs targeting candidate differentially expressed genes (DEGs) were also investigated.Results: A total of 127 significantly DEGs in patients with distant metastasis compared with patients without distant metastasis were identified. Then, four prognosis-related genes (LEP, DLX2, CLSTN2, and REG3A) were selected based on clustering analysis and survival analysis. Finally, three compounds targeting the candidate DEGs, including ajmaline, TTNPB, and dydrogesterone, were predicted to be potential drugs for COAD.Conclusions: This study revealed that distant metastasis in COAD is associated with a specific group of genes, and three existing drugs may suppress the distant metastasis of COAD.
Highlights
Distant metastasis accounts for a major proportion of cancer-related mortality, including colon carcinoma, which makes up to 10% of the global burden of cancer [1]
Among the top 30 hub genes, we found that two genes (LEP and DLX2) were significantly associated with overall survival (OS), and these genes were considered risky genes, with hazard ratio (HR) > 1 (p < 0.05; Figures 6A,B)
The results showed that Colon adenocarcinoma (COAD) patients with higher LEP expression had worse OS and disease-free survival (DFS) (p < 0.05; Figures 7A,B)
Summary
Distant metastasis accounts for a major proportion of cancer-related mortality, including colon carcinoma, which makes up to 10% of the global burden of cancer [1]. Colon adenocarcinoma (COAD) is the most common histological subtype of colon carcinoma and has a poor prognosis [2]. Previous studies of COAD focused on the prognostic models and regulators of metastasis [4, 5]. The genes exclusively expressed in metastatic COAD have yet to provide novel biomarkers and drug targets for use in the clinic. Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. The genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosisrelated genes associated with distant metastasis and develop therapeutic strategies for COAD patients
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