Department of Physiology & Biophysics, College of Medicine, Howard University, 520 W Street NW, Washington, DC, 20059, USA.
Clin Exp Med. 2024 Oct 14;24(1):239. doi: 10.1007/s10238-024-01498-7.
Gastric cancer is caused by different exogenous risk factors. Polymerase beta (POLB) is critical to repair oxidative and alkylating-induced DNA damage in genome maintenance. It is unknown whether overexpression of POLB genes in GC modulates tumor immunogenicity and plays a role in its prognostic value.
RNA-Seq of GC data retrieved from TCGA and GEO database and patient survival were compared using Kaplan-Meier statistical test. The TIMER algorithm was used to calculate the abundance of tumor-infiltrating immune cells. Furthermore, ROC analysis was applied to evaluate the prognostic value of POLB overexpression.
Our data analysis of TCGA and GEO gastric cancer genomics datasets reveals that POLB overexpression is significantly associated with intestinal subtypes of stomach cancer. In addition, POLB overexpression is associated with low expression of innate immune signaling genes. In contrast, POLB-overexpressed tumor harbors high mutation frequency and MSI score. Furthermore, POLB-overexpressed tumor with high immune score exhibits a better prognosis. Interestingly, our ROC analysis results suggested that POLB overexpression has a potential for prognostic markers for stomach cancer.
Our analysis suggests that aberrant POLB overexpression in stomach cancer impacts the diverse aspects of tumor immune microenvironment. In addition, POLB might be a potential prognosis marker and/or an attractive target for immune-based therapy in GC. However, our observation still requires further experimental-based scientific validation studies.
胃癌由不同的外源性危险因素引起。聚合酶β（POLB）对于修复基因组维持中的氧化和烷化诱导的 DNA 损伤至关重要。目前尚不清楚 GC 中 POLB 基因的过表达是否调节肿瘤免疫原性并发挥其预后价值。
使用 Kaplan-Meier 统计检验比较从 TCGA 和 GEO 数据库中检索的 GC 数据的 RNA-Seq 和患者生存情况。使用 TIMER 算法计算肿瘤浸润免疫细胞的丰度。此外，还应用 ROC 分析评估 POLB 过表达的预后价值。
我们对 TCGA 和 GEO 胃癌基因组数据集的数据分析表明，POLB 过表达与胃癌的肠型显著相关。此外，POLB 过表达与固有免疫信号基因的低表达相关。相比之下，POLB 过表达的肿瘤具有高频突变和 MSI 评分。此外，POLB 过表达的肿瘤具有高免疫评分，预后较好。有趣的是，我们的 ROC 分析结果表明，POLB 过表达具有作为胃癌预后标志物的潜力。
我们的分析表明，胃癌中异常的 POLB 过表达影响肿瘤免疫微环境的多个方面。此外，POLB 可能是 GC 免疫治疗的潜在预后标志物和/或有吸引力的靶标。然而，我们的观察结果仍需要进一步的基于实验的科学验证研究。
