Del Puerto-Nevado Laura, Fernández-Aceñero María J, Cebrián Arancha, Fatych Yuliia, Díez-Valladares Luis I, Pérez-Aguirre Elia, de la Serna Sofía, García-Botella Alejandra, Martínez-Useros Javier, García-Foncillas Jesús, Mateos-Gómez Pedro A
Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid (UAM), Madrid, Spain.
Pathology Department, Hospital Clínico San Carlos, Madrid, Spain.
Front Oncol. 2024 Oct 7;14:1433179. doi: 10.3389/fonc.2024.1433179. eCollection 2024.
DNA polymerase theta (POLQ) is a translesion synthesis polymerase essential for the repair of double strand breaks by the error-prone TMEJ (Theta Mediated End Joining) pathway. Although POLQ participates in maintaining genome stability, several studies have shown that its overexpression correlates with cancer progression and poor prognosis. Due to the fact that its role as a biomarker in pancreatic cancer remains unexplored, we aimed to study the usefulness of POLQ H-score as a prognostic factor in a pancreatic cancer patient cohort.
We evaluated gene expression using a web-based tool to deliver gene expression profiling and interactive analyses based on TCGA and GTEx (GEPIA) and we examined the POLQ immunostaining in 152 biliopancreatic cancer surgical specimens using tissue microarrays. Association with survival was evaluated by Kaplan Meier curves and uni-multivariate Cox regression.
GEPIA analysis showed statistical differences according to mRNA levels in Disease Free Survival (DFS) (log rank 0.023, HR 2.8, 0.029) and Overall Survival (OS) (log rank 0.011, HR 3.1, 0.016). For immunohistochemistry (IHC) evaluation, POLQ H-score was calculated, and showed statistical differences for OS in Kaplan Meier curves (log rank 0.001) and uni-multivariate analysis (HR 2.27; 95% CI 1.24-4.15, =0.008).
Our results indicate that POLQ is an independent prognostic factor in pancreatic cancer when analyzed by immunostaining, which is in agreement with the results shown by the gene expression analysis (GEPIA).
DNA聚合酶θ（POLQ）是一种跨损伤合成聚合酶，对于通过易出错的TMEJ（θ介导的末端连接）途径修复双链断裂至关重要。尽管POLQ参与维持基因组稳定性，但多项研究表明其过表达与癌症进展和不良预后相关。由于其在胰腺癌中作为生物标志物的作用尚未得到探索，我们旨在研究POLQ H评分作为胰腺癌患者队列预后因素的有用性。
我们使用基于网络的工具评估基因表达，以基于TCGA和GTEx（GEPIA）进行基因表达谱分析和交互式分析，并使用组织微阵列检查152例胆胰癌手术标本中的POLQ免疫染色。通过Kaplan Meier曲线和单变量及多变量Cox回归评估与生存的相关性。
GEPIA分析显示，根据无病生存期（DFS）（对数秩0.023，HR 2.8，P = 0.029）和总生存期（OS）（对数秩0.011，HR 3.1，P = 0.016）的mRNA水平存在统计学差异。对于免疫组织化学（IHC）评估，计算了POLQ H评分，其在Kaplan Meier曲线（对数秩0.00）和单变量分析（HR 2.27；95%CI 1.24 - 4.15，P = 0.008）中显示出OS的统计学差异。
我们的结果表明，通过免疫染色分析时，POLQ是胰腺癌的独立预后因素，这与基因表达分析（GEPIA）显示的结果一致。
