Abstract
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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor of the digestive system, with a 5-year survival rate of only 8% [1]
We identified the differentially expressed genes in PDAC in the The Cancer Genome Atlas (TCGA) database using Gene Expression Profiling Interactive Analysis (GEPIA) (Figure 1(a))
These differentially expressed genes were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, which indicated that these DEGs were mainly enriched in pathways involved in the extracellular matrix (ECM) and extracellular structure organization and the PI3K-Akt signaling pathway
Summary
Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor of the digestive system, with a 5-year survival rate of only 8% [1]. GLOBOCAN 2018 estimated that pancreatic cancer ranked as the seventh leading cause of cancer death worldwide, with approximately 458,918 new incidence cases and 432,242 deaths [2]. Because of its poor prognosis, newly diagnosed cases and deaths from pancreatic cancer have significantly increased at the same pace over the last few decades [2]. Surgical resection is still the most effective treatment, which significantly improves the 5-year survival rate to 20–30%. Less than 20% of all patients are eligible for resection because the majority of Disease Markers e differentially expressed genes on chromosomes. GSE62452 e gene positions are based on GRCh38.p2(NCBI).
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