Background
Duodenal carcinoma is the third cause of mortality in familial adenomatous polyposis (FAP) patients. The molecular mechanism by which FAP triggers and regulates duodenal carcinoma development was seldom studied so far.
Objective
The present study sought to use the bioinformatics approaches to provide novel insights into the molecular mechanism of FAP developing into duodenal carcinoma.
Methods
Based on GSE111156 dataset, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify differentially expressed genes (DEGs) and key gene modules, respectively. The functional enrichment analysis was conducted R package “clusterProfiler” and biological functions and pathways related to the immune system were further identified.
Results
Between adenoma tissue samples from FAP patients with and without duodenal carcinoma, 13 up-regulated genes including MIR4747, THBS1, and RNU6_62 and 113 down-regulated genes including AKR1B10, AGAP9 and AKR1C3 were identified. These DEGs were mainly involved in terpnoid metabolism. In WGCNA analysis, the blue module associated with duodenal carcinoma in FAP contained 5393 genes including 11 hub genes and was mainly related to the regulation of neuron projection development. In tissues from FAP patients with duodenal carcinoma, 32 up-regulated genes including INHBA, COL3A1, and COL1A1 and 18 down-regulated genes including MT1H, KIAA1324, and HMGCS2 were screened between adenocarcinoma and normal tissues and were also significantly related to terpnoid metabolism. Between adenocarcinoma and adenoma tissues, we screened 171 up-regulated genes including CEACAM5, SLC2A1 and PKMRNU6_62 and 238 downregulated genes including RBP2, GSTA5 and SST, which were mainly involved in extracellular matrix organization. WGCNA revealed that the darkorange module associated with adenocarcinoma contained 554 genes including 19 hub genes and was involved in extracellular matrix organization and focal adhesion. Further identification of immune related processes showed that leukocyte migration was the process mostly involved in the transition of normal tissue into adenoma while neutrophil-mediated immunity was the most dysregulated in adenocarcinoma.
Conclusion
The present study preliminary uncovered the mechanism behind initiation and progression in duodenal carcinoma in FAP, and provided some scientific information for exploring novel therapeutic strategies for FAP patients with duodenal carcinoma.