Integrated Analysis of DNA Repair Genes Identifies SLC6A1 as a New Marker for the Clinical Outcome of Patients with Colorectal Cancer

Abstract

Colorectal cancer (CRC) remains an important malignancy worldwide with poor prognosis. It has been known that DNA repair genes are involved in the development and progression of various tumors. Therefore, the purpose of this study was to explore DNA repair gene-based prognostic biomarkers for CRC. In this study, the expressing pattern and prognostic values of DNA repair genes in CRC patients were analyzed using TCGA database. GO and KEGG enrichment analyses were conducted to clarify the functional roles of dysregulated genes. We observed 358 differentially expressed DNA repair genes in CRC specimens, including 84 downregulated genes and 275 upregulated genes. 36 survival-related DNA repair genes were correlated with CRC patients’ five-year survival, including 6 low-risk genes and 30 high-risk genes. Among the 10 overlapping genes, we focused on SLC6A1 which was highly expressed in CRC, and multivariate analysis confirmed that SLC6A1 expression as well as age and clinical stage could be regarded as an independent predicting factor for CRC prognosis. KEGG assays revealed that SLC6A1 may influence the clinical progression via regulating TGF-beta and PI3K-Akt signaling pathways. In addition, we observed that SLC6A1 was negatively regulated by SLC6A1 methylation, leading to its low expression in CRC specimens. Overall, SLC6A1 is upexpressed in CRC and can be used as a marker of poor prognosis in CRC patients.