Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, China.
BMC Med Genomics. 2023 Feb 20;16(1):27. doi: 10.1186/s12920-023-01459-1.
This study aimed to investigate the potential prognostic value of DNA damage repair genes (DDRGs) in esophageal squamous cell carcinoma (ESCC) and their relationship with immune-related characteristics.
We analyzed DDRGs of the Gene Expression Omnibus database (GSE53625). Subsequently, the GSE53625 cohort was used to construct a prognostic model based on least absolute shrinkage and selection operator regression, and Cox regression analysis was used to construct a nomogram. The immunological analysis algorithms explored the differences between the potential mechanism, tumor immune activity, and immunosuppressive genes in the high- and low-risk groups. Of the prognosis model-related DDRGs, we selected PPP2R2A for further investigation. Functional experiments were conducted to evaluate the effect on ESCC cells in vitro.
A 5-DDRG (ERCC5, POLK, PPP2R2A, TNP1 and ZNF350) prediction signature was established for ESCC, stratifying patients into two risk groups. Multivariate Cox regression analysis showed that the 5-DDRG signature was an independent predictor of overall survival. Immune cells such as CD4 T cells and monocytes displayed lower infiltration levels in the high-risk group. Additionally, the immune, ESTIMATE, and stromal scores in the high-risk group were all considerably higher than those in the low-risk group. Functionally, knockdown of PPP2R2A significantly suppressed cell proliferation, migration and invasion in two ESCC cell lines (ECA109 and TE1).
The clustered subtypes and prognostic model of DDRGs could effectively predict the prognosis and immune activity of ESCC patients.
本研究旨在探讨 DNA 损伤修复基因（DDRGs）在食管鳞状细胞癌（ESCC）中的潜在预后价值及其与免疫相关特征的关系。
我们分析了基因表达综合数据库（GSE53625）中的 DDRGs。随后，使用 GSE53625 队列基于最小绝对收缩和选择算子回归构建预后模型，并进行 Cox 回归分析构建列线图。免疫分析算法探讨了高低风险组之间潜在机制、肿瘤免疫活性和免疫抑制基因的差异。在与预后模型相关的 DDRGs 中，我们选择 PPP2R2A 进行进一步研究。进行功能实验以评估其对体外 ESCC 细胞的影响。
建立了一个包含 5 个 DDRG（ERCC5、POLK、PPP2R2A、TNP1 和 ZNF350）的 ESCC 预测标志，将患者分为两个风险组。多变量 Cox 回归分析显示，5-DDRG 标志是总生存的独立预测因子。高风险组中 CD4 T 细胞和单核细胞等免疫细胞的浸润水平较低。此外，高风险组的免疫、ESTIMATE 和基质评分均显著高于低风险组。功能上，PPP2R2A 的敲低显著抑制了两种 ESCC 细胞系（ECA109 和 TE1）的细胞增殖、迁移和侵袭。
DDRGs 的聚类亚型和预后模型可以有效预测 ESCC 患者的预后和免疫活性。
