Novel acetylation-related gene signatures for predicting the prognosis of patients with colorectal cancer.

Abstract

Histone acetylation may affect the tumorigenesis and prognosis of colorectal cancer (CRC). However, there is still a lack of studies exploring the effect of acetylation-related genes on the prognosis of CRC. To explore the role of acetylation-related genes in CRC prognosis using bioinformatics strategies, the expression data and survival information of CRC patients were collected from the Gene Expression Omnibus. The Molecular Signatures Database was used to select acetylation-related genes. Univariate and least absolute shrinkage and selection operator regression analyses were used to screen prognostic genes. Kaplan-Meier curves were plotted for survival analysis. Cibersort and pRRophetics were used to analyze immune infiltration and predict drug sensitivity, respectively. By implementing independent prognostic factors, a nomogram model was constructed. The result showed that a total of 48 prognostic genes which screened from the acetylation-related gene set were mainly enriched in ABC transporters and acetylation/deacetylation-related pathways. Three gene signatures (SDR16C5, MEAF6, and SOX4) were further defined, and a prognostic model was constructed that showed high sensitivity and specificity for predicting CRC prognosis in both training and validation cohorts. Patients with different prognostic risks also presented differential expression of gene signatures, infiltration of activated CD4 memory T cells, and drug sensitivity to bicalutamide, gefitinib, Lenalidomide, and imatinib. The nomogram suggested the potential of a risk score-based model in predicting 1- and 2-year survival in patients with CRC. In conclusion, we proposed three gene signatures from an acetylation-related gene set as potential targets for epigenetic therapy and constructed a prognostic model for CRC.