Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
Key Laboratory of Anticancer Drugs and Biotherapy, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
Dis Markers. 2020 Aug 31;2020:8825997. doi: 10.1155/2020/8825997. eCollection 2020.
Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor. The immune profile of PDAC and the immunologic milieu of its tumor microenvironment (TME) are unique; however, the mechanism of how the TME engineers the carcinogenesis of PDAC is not fully understood. This study is aimed at better understanding the relationship between the immune infiltration of the TME and gene expression and identifying potential prognostic and immunotherapeutic biomarkers for PDAC. Analysis of data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases identified differentially expressed genes (DEGs), including 159 upregulated and 53 downregulated genes. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment were performed and showed that the DEGs were mainly enriched for the PI3K-Akt signaling pathway and extracellular matrix organization. We used the cytoHubba plugin of Cytoscape to screen out the most significant ten hub genes by four different models (Degree, MCC, DMNC, and MNC). The expression and clinical relevance of these ten hub genes were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas, respectively. High expression of nine of the hub genes was positively correlated with poor prognosis. Finally, the relationship between these hub genes and tumor immunity was analyzed using the Tumor Immune Estimation Resource. We found that the expression of SPARC, COL6A3, and FBN1 correlated positively with infiltration levels of six immune cells in the tumors. In addition, these three genes had a strong coexpression relationship with the immune checkpoints. In conclusion, our results suggest that nine upregulated biomarkers are related to poor prognosis in PDAC and may serve as potential prognostic biomarkers for PDAC therapy. Furthermore, SPARC, COL6A3, and FBN1 play an important role in tumor-related immune infiltration and may be ideal targets for immune therapy against PDAC.
胰腺导管腺癌 (PDAC) 是一种极其恶性的肿瘤。PDAC 的免疫特征及其肿瘤微环境 (TME) 的免疫环境是独特的；然而，TME 如何设计 PDAC 的癌变机制尚不完全清楚。本研究旨在更好地了解 TME 的免疫浸润与基因表达之间的关系，并确定 PDAC 的潜在预后和免疫治疗生物标志物。对来自癌症基因组图谱 (TCGA) 和基因表达综合数据库 (GEO) 的数据进行分析，确定差异表达基因 (DEGs)，包括 159 个上调基因和 53 个下调基因。进行基因本体论分析和京都基因与基因组百科全书富集分析，结果表明 DEGs 主要富集在 PI3K-Akt 信号通路和细胞外基质组织中。我们使用 Cytoscape 的 cytoHubba 插件，通过四种不同的模型 (Degree、MCC、DMNC 和 MNC) 筛选出最重要的十个枢纽基因。使用基因表达谱交互式分析 (GEPIA) 和人类蛋白质图谱分别验证了这十个枢纽基因的表达和临床相关性。这十个枢纽基因中，有九个的高表达与预后不良呈正相关。最后，使用肿瘤免疫估计资源分析了这些枢纽基因与肿瘤免疫的关系。我们发现，SPARC、COL6A3 和 FBN1 的表达与肿瘤中六种免疫细胞的浸润水平呈正相关。此外，这三个基因与免疫检查点之间存在强烈的共表达关系。总之，我们的研究结果表明，九个上调的生物标志物与 PDAC 的不良预后相关，可能成为 PDAC 治疗的潜在预后生物标志物。此外，SPARC、COL6A3 和 FBN1 在肿瘤相关免疫浸润中发挥重要作用，可能是针对 PDAC 的免疫治疗的理想靶点。
