Abstract
IntroductionMacrophage phenotype switch plays a vital role in the progression of malignancies. We aimed to build a prognostic signature by exploring the expression pattern of macrophage phenotypic switch related genes (MRGs) in the Cancer Genome Atlas (TCGA)—pancreatic adenocarcinoma (PAAD), Genotype-Tissue Expression (GTEx)-Pancreas, and Gene Expression Omnibus (GEO) databases.MethodsWe identified the differentially expressed genes between the PAAD and normal tissues. We used single factor Cox proportional risk regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and multivariate Cox proportional hazard regression analysis to establish the prognosis risk score by the MRGs. The relationships between the risk score and immune landscape, “key driver” mutations and clinicopathological factors were also analyzed. Gene-set enrichment analysis (GSEA) analysis was also performed.ResultsWe detected 198 differentially expressed MRGs. The risk score was constructed based on 9 genes (KIF23, BIN1, LAPTM4A, ERAP2, ATP8B2, FAM118A, RGS16, ELMO1, RAPGEFL1). The median overall survival time of patients in the low-risk group was significantly longer than that of patients in the high-risk group (P < 0.001). The prognostic value of the risk score was validated in GSE62452 dataset. The prognostic performance of nomogram based on risk score was superior to that of TNM stage. And GSEA analysis also showed that the risk score was closely related with P53 signaling pathway, pancreatic cancer and T cell receptor signaling pathway. qRT-PCR assay showed that the expressions of the 9 MRGs in PDAC cell lines were higher than those in human pancreatic ductal epithelium cell line.ConclusionsThe nine gene risk score could be used as an independent prognostic index for PAAD patients. Further studies validating the prognostic value of the risk score are warranted.
Highlights
IntroductionWe aimed to build a prognostic signature by exploring the expression pattern of macrophage phenotypic switch related genes (MRGs) in the Cancer Genome Atlas (TCGA)—pancreatic adenocarcinoma (PAAD), Genotype-Tissue Expression (GTEx)Pancreas, and Gene Expression Omnibus (GEO) databases
Macrophage phenotype switch plays a vital role in the progression of malignancies
198 differentially expressed macrophage phenotypic switch related genes (MRGs) meeting the criteria as |log(foldchange)| > 1 and false discovery rate (FDR) < 0.05 by the pooled analysis of the Cancer Genome Atlas (TCGA)-pancreatic adenocarcinoma (PAAD) and Genotype-Tissue Expression (GTEx)-pancreas databases were obtained (Figure 1A, Table S2)
Summary
We aimed to build a prognostic signature by exploring the expression pattern of macrophage phenotypic switch related genes (MRGs) in the Cancer Genome Atlas (TCGA)—pancreatic adenocarcinoma (PAAD), Genotype-Tissue Expression (GTEx)Pancreas, and Gene Expression Omnibus (GEO) databases. Pancreatic ductal adenocarcinoma (PDAC), with an estimated 5year overall survival rate less than 10%, is the fourth leading cause of cancer-related mortality in the world [1]. The lack of effective systematic therapies and useful prognostic indexes deteriorates the dismal prognosis of pancreatic cancer patients [2]. With the development of high-throughput technologies, molecular characterization may shed light on newer therapeutic targets [3]. It is essential to identify molecular prognostic factors of pancreatic cancer which aid in rational stratification of patients according to the clinical prognosis as well as in providing potentially therapeutic targets [4]
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