Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China (mainland).
Department of Gastrointestinal Endoscopy, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China (mainland).
Med Sci Monit. 2023 Mar 11;29:e938785. doi: 10.12659/MSM.938785.
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) accounts for 85% of pancreatic carcinoma cases. Patients with PDAC have a poor prognosis. The lack of reliable prognostic biomarkers makes treatment challenging for patients with PDAC. Using a bioinformatics database, we sought to identify prognostic biomarkers for PDAC. MATERIAL AND METHODS Using proteomic analysis of the Clinical Proteomics Tumor Analysis Consortium (CPTAC) database, we were able to identify core differential proteins between early and advanced pancreatic ductal adenocarcinoma tissue, and then we used survival analysis, Cox regression analysis, and area under the ROC curves to screen for more significant differential proteins. Additionally, the Kaplan-Meier plotter database was utilized to determine the relationship between prognosis and immune infiltration in PDAC. RESULTS We identified 378 differential proteins in early (n=78) and advanced stages (n=47) of PDAC (P<0.05). PLG, COPS5, FYN, ITGB3, IRF3, and SPTA1 served as independent prognostic factors of patients with PDAC. Patients with higher COPS5 expression had shorter overall survival (OS) and recurrence-free survival, and those with higher PLG, ITGB3, and SPTA1, and lower FYN and IRF3 expression had shorter OS. More importantly, COPS5, IRF3 were negatively associated with macrophages and NK cells, but PLG, FYN, ITGB3, and SPTA1 were positively related to the expression of CD8+ T cells and B cells. COPS5 affected the prognosis of PDAC patients by acting on B cells, CD8+ T cells, macrophages, and NK cells immune infiltration, while PLG, FYN, ITGB3, IRF3, and SPTA1 affected PDAC patient prognosis through some immune cells. CONCLUSIONS PLG, COPS5, FYN, IRF3, ITGB3 and SPTA1 could be potential immunotherapeutic targets and valuable prognostic biomarkers of PDAC.
胰腺导管腺癌（PDAC）占胰腺癌病例的 85%。PDAC 患者预后较差。缺乏可靠的预后生物标志物使得 PDAC 患者的治疗具有挑战性。本研究使用生物信息学数据库，旨在鉴定 PDAC 的预后生物标志物。
我们使用临床蛋白质组肿瘤分析联盟（CPTAC）数据库的蛋白质组分析，鉴定了早期和晚期胰腺导管腺癌组织之间的核心差异蛋白，然后使用生存分析、Cox 回归分析和 ROC 曲线下面积筛选更显著的差异蛋白。此外，我们还利用 Kaplan-Meier 绘谱器数据库确定了 PDAC 中预后与免疫浸润的关系。
我们在 PDAC 的早期（n=78）和晚期（n=47）阶段鉴定到 378 个差异蛋白（P<0.05）。PLG、COPS5、FYN、ITGB3、IRF3 和 SPTA1 是 PDAC 患者独立的预后因素。COPS5 表达水平较高的患者总生存期（OS）和无复发生存期（RFS）更短，而 PLG、ITGB3 和 SPTA1 表达水平较高，FYN 和 IRF3 表达水平较低的患者 OS 更短。更重要的是，COPS5 和 IRF3 与巨噬细胞和 NK 细胞呈负相关，而 PLG、FYN、ITGB3 和 SPTA1 与 CD8+T 细胞和 B 细胞的表达呈正相关。COPS5 通过作用于 B 细胞、CD8+T 细胞、巨噬细胞和 NK 细胞免疫浸润来影响 PDAC 患者的预后，而 PLG、FYN、ITGB3、IRF3 和 SPTA1 则通过某些免疫细胞影响 PDAC 患者的预后。
PLG、COPS5、FYN、IRF3、ITGB3 和 SPTA1 可能是 PDAC 的潜在免疫治疗靶点和有价值的预后生物标志物。
