ArticleTranslational oncology2019
Immune-related somatic mutation genes are enriched in PDACs with diabetes.
Article in Translational oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Epidemiological Trends and Shared Molecular Signatures of Pancreatic Ductal Adenocarcinoma and Diabetes: An Integrative Analysis Based on Global Burden of Disease and Gene Expression Omnibus Datasets.Journal of Cancer · 2026Article
- Potential Benefits of Antioxidant Phytochemicals in Type 2 Diabetes.Molecules (Basel, Switzerland) · 2023Review
- Proteogenomic insights into the biology and treatment of pancreatic ductal adenocarcinoma.Journal of hematology & oncology · 2022Article
- Mortality and glycemic control among patients with acute and chronic myeloid leukemia and diabetes: a case-control study.Future science OA · 2020Article
- Genomic Analysis Reveals Novel Specific Metastatic Mutations in Chinese Clear Cell Renal Cell Carcinoma.BioMed research international · 2020Article
- The Roles of Frequently Mutated Genes of Pancreatic Cancer in Regulation of Tumor Microenvironment.Technology in cancer research & treatmentReview
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Authors and funding
11 authors.
Funding
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Abstract
The bidirectional interaction between pancreatic cancer (PanCa) and diabetes has been confirmed by epidemiological studies, but until now, the underlying molecular mechanisms for this connection is not fully understood yet. Here, we analyzed the clinical and genomic data of 26 pancreatic ductal adenocarcinoma (PDAC) patients without diabetes, and six diabetic PDAC patients, whose tumors underwent targeted next-generation sequencing (551 cancer-related genes included). Ingenuity Pathway Analysis (IPA) was performed to investigate genetic alterations and biological consequences associated with PDACs with or without diabetes. We identified 345 somatic mutations of 153 genes in test cohort and a positive association between diabetes duration and somatic mutation burden. KRAS, TP53, and SMAD4 were the top3 commonly mutated genes at a similar frequency compared to the Cancer Genome Atlas (TCGA) data. Several novel but infrequent mutations in other genes (MDC1, PRB2, and PRB4) were also found. Besides, 13 mutated genes (PIK3CD, SNCAIP, IRF4, HLA-A, NOTCH4, PIM1, ETV6, B2M, CD70, PRDM14, TGFBR1, FLT1, and PARP2) were uniquely found in the diabetic group, mainly involved in immune-related pathways. Further targeted sequencing of these genes in an independent validation cohort (n = 50) revealed significant enrichment in the diabetic group (n = 18, P = 2.6964E-08). Long-standing diabetes (≥3-year duration) may induce increasing somatic mutations with time, facilitating tumor initiation. Gene mutants associated with immune-related pathways could be used to distinguish the diabetic PDAC patients from the non-diabetic cases and allow more selective treatment.
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