Abstract
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.
Highlights
Pancreatic cancer has one of the highest mortality rates of any cancer type, with an overall five-year survival (OS) rate of less than 5%
We found a higher degree of immune infiltration of CD8Tex in the tumour microenvironment of diabetic pancreatic cancer patients compared to normal pancreatic cancer
Overexpression analysis and Gene Set Enrichment Analysis (GSEA) analysis, we found that immune and inflammation-related signalling pathways were activated in the tumour tissues of diabetic pancreatic cancer patients relative to the normal pancreatic cancer patients
Summary
Pancreatic cancer has one of the highest mortality rates of any cancer type, with an overall five-year survival (OS) rate of less than 5%. Numerous studies have shown that diabetes is a major risk factor for the development of pancreatic cancer. Despite the fact that diabetes affects the recovery of patients after radiotherapy, chemotherapy and surgical resection of pancreatic cancer, there is no significant difference in the overall survival of pancreatic cancer patients with diabetes [5, 6]. This conclusion is still controversial, no well-established theory is still available to explain the phenomenon. There is still no practical theory to explain this phenomenon
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