摘要： 目的 探讨分泌磷蛋白1（SPP1）在胰腺导管腺癌中的表达与预后的关系及其作用机制。方法 应用高通量基因表达数据库（GEO）、基因表达谱动态分析（GEPIA）数据库，挖掘分析胰腺导管腺癌中SPP1的表达情况，并应用Kaplan-Meier Plotter数据库进行生存分析，通过DAVID及STRING在线分析SPP1可能参与调控的信号通路，构建蛋白质-蛋白质相互作用网络。采用免疫组化方法检测56例胰腺导管腺癌和39例正常胰腺导管组织中SPP1的表达情况。采用Kaplan-Meier法进行生存分析。结果 GEPIA及GEO数据库中与正常对照组织比较，胰腺导管腺癌中SPP1呈现高表达（P < 0.01）。免疫组化结果显示SPP1在胰腺导管腺癌中的阳性表达率显著高于正常胰腺导管组织（P < 0.01），并且与胰腺导管腺癌的分化程度相关（P < 0.05），组织分化程度越低，SPP1阳性表达率越高（r=0.338，P < 0.05）。Kaplan-Meier Plotter及GEPIA数据库生存分析结果显示，与SPP1低表达患者比较，SPP1高表达胰腺癌患者的总生存时间显著减少（P < 0.05）。Kaplan-Meier法分析结果证实SPP1阳性表达率高的患者预后较差（P < 0.01）。DAVID在线富集分析显示，SPP1表达与细胞黏附、细胞外基质相互作用等信号通路相关。结论 胰腺导管腺癌中SPP1呈现高表达，且SPP1高表达患者预后欠佳，其作用机制可能是SPP1参与了细胞黏附、细胞外基质相互作用等信号通路，进而促进了肿瘤的增殖、侵袭和转移。

基于生物信息学分析胰腺导管腺癌中SPP1的表达与预后的关系及其作用机制

迂金洋, 杨向红

中国医科大学附属盛京医院病理科, 沈阳 110004

收稿日期:2022-08-17出版日期:2023-02-28发布日期:2023-02-04
通讯作者:杨向红E-mail:xhyang4933@vip.sina.com
作者简介:迂金洋(1991-),女,医师,硕士研究生.
基金资助:国家自然科学基金（81773108）


关键词: 胰腺导管腺癌, 分泌磷蛋白1, 生物信息学, 预后, 作用机制
Abstract: Objective To investigate SPP1 expression in pancreatic ductal adenocarcinoma tissues, analyze the relationship between SPP1 expression and patient prognosis, and discuss its potential mechanism. Methods Bioinformatics online analysis sites such as Gene Expression Omnibus (GEO), and Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze SPP1 expression in pancreatic ductal adenocarcinoma. Kaplan-Meier Plotter was used for survival analysis. DAVID and STRING was adopted to explore SPP1 protein interactions and signaling pathways SPP1 participates in. Immunohistochemical staining was performed to detect SPP1 expression in 56 pancreatic ductal adenocarcinoma tissue samples and 39 pancreatic ductal tissue samples. The Kaplan-Meier model was applied in prognosis analysis. Results Data from the GEPIA and GEO databases showed that SPP1 was highly expressed in pancreatic ductal adenocarcinoma tissues compared to normal pancreatic ductal tissues (P < 0.01), which was proved by immunohistochemical staining (P < 0.01). The positive expression rate was statistically correlated with histological differentiation of pancreatic ductal adenocarcinoma (P < 0.05); lower differentiation resulted in a higher positive expression rate (r=0.338, P < 0.05). Survival analysis of Kaplan-Meier Plotter and the GEPIA database showed that, compared with the low expression group, the overall survival time of patients with pancreatic cancer in the SPP1 high expression group was significantly reduced (P < 0.05), which was further confirmed by our survival data (P < 0.01). Online DAVID enrichment analysis showed that SPP1 was related to signaling pathways such as cell adhesion and extracellular matrix interaction. Conclusion SPP1 was highly expressed in pancreatic ductal adenocarcinoma tissue, and patients with increased SPP1 expression showed poor prognosis. A possible mechanism is that SPP1 participates in signaling pathways such as cell adhesion and extracellular matrix interaction, thereby promoting tumor proliferation, invasion, and metastasis.
Key words: pancreatic ductal adenocarcinoma, secreted phosphoprotein 1, bioinformatics, prognosis, mechanism
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