4.7 Article

Immune Infiltration of CD8+T Cells in Patients With Diabetic Pancreatic Cancer Reduces the Malignancy of Cancer Tissues: An In Silico Study

Journal

FRONTIERS IN ENDOCRINOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2021.826667

Keywords

pancreatic cancer; diabetes; tumor microenvironment; miRNA-mRNA regulation network; immune therapy

Funding

  1. National Natural Science Foundation of China [81970717, 82000740, 82170845]
  2. Key Research & Development Program of Jiangsu Province [BE2018742]

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This study found that immune-related signal transduction pathways are activated in diabetic pancreatic cancer patients, with high infiltration scores of CD8+ T cells and low infiltration scores of malignant tumor cells. A Bayesian classifier can distinguish diabetic pancreatic cancer patients from non-diabetic pancreatic cancer patients based on 10 signature genes. The miRNA-mRNA regulatory network may be the main cause of the differences in the tumor inflammatory microenvironment between the two groups of patients.
BackgroundAlthough the functional damage of the diabetic pancreas can affect the postoperative recovery of pancreatic cancer patients, there is no significant difference in the prognosis of pancreatic cancer patients with a history of diabetes and ordinary pancreatic cancer patients. There is still no practical theory to explain this phenomenon. Materials and MethodThe mRNA expression profile data of 141 cases and 51 cases with clinical data of diabetes status were obtained from the TCGA database and the GEO database, respectively. The CRA001160 data set was obtained in the TISCH database. The Seurat was used to process single-cell expression profile sequencing data. The Cibersortx was used to construct a feature matrix of single-cell sequencing data and to deconvolve Bulk-RNAseq data to obtain each pancreatic cancer patients' tumour invasion score. TIDE was used to assess the immune escape potential of the tumour. MiRNet was used to construct the miRNA-mRNA regulatory network. ResultCompared with regular pancreatic cancer patients, the immune-related signal transduction pathways in diabetic pancreatic cancer patients are in an activated state. In patients with diabetic pancreatic cancer, the infiltration score of CD8+ T cells is high, and the infiltration score of corresponding malignant tumour cells is low. The Bayesian classifier can distinguish diabetic pancreatic cancer patients from non-diabetic pancreatic cancer patients based on 10 signature genes. The miRNA-mRNA regulatory network suggests that regulation by miRNA can influence mRNA expression and thus prognostic survival of pancreatic cancer patients. ConclusionThe activation of inflammatory-related signalling pathways in diabetic pancreatic cancer patients increases the immune infiltration of CD8+ T cells in cancer patients and reduces the development of malignant tumour tissues. The expression of 10 signature genes allowed the diagnosis of diabetic and non-diabetic pancreatic cancer patients. The miRNA-mRNA regulatory network may be the main cause of the differences in the tumour inflammatory microenvironment between the two groups of patients. These findings help us further understand the immune microenvironment of patients with diabetic pancreatic cancer.

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