Identification of characteristic markers correlated with Th2 cell infiltration and metabolism molecular subtype in pancreatic adenocarcinoma

Abstract

Background: Pancreatic adenocarcinoma, the deadliest malignant cancer, has gradually become the third leading cause of cancer-related death. Multidisciplinary therapy has been difficult to implement because of the particularity of pancreatic adenocarcinoma. Research has increasingly indicated the significance of metabolic adaption in pancreatic adenocarcinoma. The difference in metabolism may influence immune cell infiltration in pancreatic adenocarcinoma. Novel immune-related metabolism biomarkers are needed to improve the therapeutic outcomes of existing targeted therapies.Methods: We enrolled whole-genome sequencing data and clinical information about 168 pancreatic adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database, other pancreatic adenocarcinoma samples, and clinical information from other cohorts. We used the gene set variation analysis (GSVA) package to calculate feature score, the weighted gene co-expression network analysis (WGCNA) and randomSurvivalForest package to screen hub genes, the ConsenClusterPlus package to classify subtypes, the pRRopthetic package to evaluate drug sensibility, the maftools package to analyze mutation information and the Seurat package to analyze single cell sequencing data.Results: We revealed the prognosis significance of Th2 cell infiltration, classified two subtypes based on hub genes, compared immune cell infiltration, substance metabolism, cellular processes, gene mutation, and copy number variation (CNV) between subtypes and explored the clinical and biological features of Th2 cell infiltration. Conclusions:We displayed the poor prognosis significance of Th2 cell infiltration and the significant difference of simple nucleotide polymorphism, CNV, natural killer (NK) CD56 bright cell infiltration, substance metabolism, autophagy and necroptosis between subtypes. Additionally, we discovered the sensitivity difference of chemotherapy drug and the Th2 cell infiltration changes after chimeric antigen receptor T cells (CAR-T) cell therapy and radiotherapy and explored the differences between normal liver and metastatic liver tissues of pancreatic adenocarcinoma patients.