Abstract

PurposeThe current clinical classification of pancreatic ductal adenocarcinoma (PDAC) cannot well predict the patient’s possible response to the treatment plan, nor can it predict the patient’s prognosis. We use the gene expression patterns of PDAC patients to reveal the heterogeneity of the tumor microenvironment of pancreatic cancer and analyze the differences in the prognosis and immunotherapy response of different immune subtypes.MethodsFirstly, use ICGC’s PACA-AU PDAC expression profile data, combined with the ssGSEA algorithm, to analyze the immune enrichment of the patient’s tumor microenvironment. Subsequently, the spectral clustering algorithm was used to extract different classifications, the PDAC cohort was divided into four subtypes, and the correlation between immune subtypes and clinical characteristics and survival prognosis was established. The patient’s risk index is obtained through the prognostic prediction model, and the correlation between the risk index and immune cells is prompted.ResultsWe can divide the PDAC cohort into four subtypes: immune cell and stromal cell enrichment (Immune-enrich-Stroma), non-immune enrichment but stromal cell enrichment (Non-immune-Stroma), immune-enriched Collective but non-matrix enrichment (Immune-enrich-non-Stroma) and non-immune enrichment and non-stromal cell enrichment (Non-immune-non-Stroma). The five-year survival rate of immune-enrich-Stroma and non-immune-Stroma of PACA-CA is quite different. TCGA-PAAD’s immune-enrich-Stroma and immune-enrich-non-Stroma groups have a large difference in productivity in one year. The results of the correlation analysis between the risk index and immune cells show that the patient’s disease risk is significantly related to epithelial cells, megakaryocyte-erythroid progenitor (MEP), and Th2 cells.ConclusionThe tumor gene expression characteristics of pancreatic cancer patients are related to immune response, leading to morphologically recognizable PDAC subtypes with prognostic/predictive significance.

Highlights

  • Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignant neoplasms around the world [1–4], and its genetic and phenotypic heterogeneity makes generally effective therapies ineffective [5–9]

  • The results of the correlation analysis between the risk index and immune cells show that the patient’s disease risk is significantly related to epithelial cells, megakaryocyteerythroid progenitor (MEP), and Th2 cells

  • The tumor gene expression characteristics of pancreatic cancer patients are related to immune response, leading to morphologically recognizable PDAC subtypes with prognostic/predictive significance

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Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignant neoplasms around the world [1–4], and its genetic and phenotypic heterogeneity makes generally effective therapies ineffective [5–9]. The salient feature of pancreatic cancer is that it has an immunosuppressive microenvironment, the prognosis of patients is poor, and most of the patients’ tumors will metastasize [10, 11]. Research on the immune microenvironment of pancreatic cancer may help improve the therapeutic effect [12, 13]. By detecting the expression of anti-tumor immune genes, markers that can predict patient response to treatment have been screened [14]. We have a better understanding of the molecular mechanism and genetic background of pancreatic cancer, the 5-year survival rate for this disease is approximately 10% in the USA [19]. It is necessary to identify new biomarkers and explore new treatment approaches to provide more and more effective references for overcoming the immunosuppressive mechanism in the pancreatic cancer microenvironment

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