Department of Oncology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiangs, China.
Department of Cardiothoracic Surgery, Yi Xing People's Hospital, No.75, Tongzhenguan Road, Yixing, Jiangsu, China.
Hum Cell. 2022 Jul;35(4):1159-1173. doi: 10.1007/s13577-022-00720-6. Epub 2022 May 23.
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.
组蛋白乙酰化可能影响结直肠癌（CRC）的发生和预后。然而，目前仍缺乏研究探讨与乙酰化相关的基因对 CRC 预后的影响。为了使用生物信息学策略探讨与乙酰化相关的基因在 CRC 预后中的作用，从基因表达综合数据库中收集了 CRC 患者的表达数据和生存信息。使用分子特征数据库选择与乙酰化相关的基因。单变量和最小绝对收缩和选择算子回归分析用于筛选预后基因。绘制 Kaplan-Meier 曲线进行生存分析。Cibersort 和 pRRophetics 分别用于分析免疫浸润和预测药物敏感性。通过实施独立预后因素，构建了列线图模型。结果显示，从与乙酰化相关的基因集中筛选出的 48 个预后基因主要富集在 ABC 转运体和乙酰化/去乙酰化相关途径中。进一步定义了三个基因特征（SDR16C5、MEAF6 和 SOX4），并构建了一个预后模型，该模型在训练和验证队列中均显示出对 CRC 预后的高敏感性和特异性。不同预后风险的患者还表现出基因特征的差异表达、活化的 CD4 记忆 T 细胞浸润和对比卡鲁胺、吉非替尼、来那度胺和伊马替尼的药物敏感性差异。该列线图提示基于风险评分的模型在预测 CRC 患者 1 年和 2 年生存率方面具有潜在价值。总之，我们从与乙酰化相关的基因集中提出了三个基因特征作为表观遗传治疗的潜在靶点，并构建了一个 CRC 的预后模型。
