Department of Critical Care Medicine, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China (mainland).
Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China (mainland).
Med Sci Monit. 2021 Nov 20;27:e933443. doi: 10.12659/MSM.933443.
BACKGROUND Pancreatic adenocarcinoma (PAAD) is one of the deadliest types of cancer. In the early stages, patients often have atypical symptoms, making diagnosis difficult. The prognosis of diagnosed patients is very poor and treating PAAD is challenging. Therefore, determining reliable risk factors related to PAAD development is critical for improving patient prognosis. E2F family transcription factors (TFs) are essential regulators of DNA synthesis and cell cycle progression in eukaryotic cells, and they have been identified as prognostic biomarkers associated with multiple cancer types. However, further research is necessary to establish the prognostic relevance of these TFs in PAAD patients. MATERIAL AND METHODS We assessed PAAD patient transcriptional and outcome data using the TIMER, ONCOMINE, STRING, GEPIA, cBioPortal, Kaplan-Meier Plotter, GSCALite, and starBase databases. RESULTS PAAD tumor tissues exhibited increased expression of E2F1/3/5/7/8 relative to that in normal tissues, while the expression of E2F2/3/6/8 was associated with a more advanced tumor stage. Survival analyses indicated that PAAD patients expressing higher levels of E2F1/2/3/7/8 exhibited shorter overall survival (OS) and disease-free survival (DFS) than patients expressing lower levels of these TFs. In addition, E2F4 and E2F6 overexpression was associated with poorer DFS and OS, respectively. We also found that the expression of E2Fs was significantly correlated with immune infiltrates, including CD8+ T cells, CD4+ T cells, B cells, dendritic cells, neutrophils, and macrophages. CONCLUSIONS Our study may provide new insights into the optimal choice of immunotherapy and promising novel targets for therapeutic intervention in PAAD patients.
胰腺导管腺癌（PAAD）是最致命的癌症类型之一。在早期阶段，患者常出现非典型症状，导致诊断困难。确诊患者的预后非常差，治疗 PAAD 极具挑战性。因此，确定与 PAAD 发展相关的可靠风险因素对于改善患者预后至关重要。E2F 家族转录因子（TFs）是真核细胞中 DNA 合成和细胞周期进程的重要调节因子，它们已被确定为与多种癌症类型相关的预后生物标志物。然而，需要进一步的研究来确定这些 TFs 在 PAAD 患者中的预后相关性。
我们使用 TIMER、ONCOMINE、STRING、GEPIA、cBioPortal、Kaplan-Meier Plotter、GSCALite 和 starBase 数据库评估了 PAAD 患者的转录组和结局数据。
与正常组织相比，PAAD 肿瘤组织中 E2F1/3/5/7/8 的表达增加，而 E2F2/3/6/8 的表达与更晚期的肿瘤分期相关。生存分析表明，表达更高水平 E2F1/2/3/7/8 的 PAAD 患者的总生存期（OS）和无病生存期（DFS）短于表达较低水平这些 TFs 的患者。此外，E2F4 和 E2F6 的过表达分别与较差的 DFS 和 OS 相关。我们还发现，E2Fs 的表达与免疫浸润物（包括 CD8+T 细胞、CD4+T 细胞、B 细胞、树突状细胞、中性粒细胞和巨噬细胞）显著相关。
我们的研究可能为 PAAD 患者的免疫治疗提供新的见解，并为治疗干预提供有前途的新靶点。
