Deciphering the Role of Complement System Genes in Pancreatic Cancer Susceptibility and Prognosis
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Pancreatic ductal adenocarcinoma (PDAC) genetic susceptibility is partially identified. The complement system (CS) influences carcinogenesis and participates in immunological defense and homeostasis; however, its role in PDAC genetic susceptibility and prognosis is underexplored.
Methods
The association of SNPs within 111 CS-related genes with PDAC risk was assessed in the PanGenEU study and validated in the UKBiobank. We investigated the association between the CS-related gene variation and PDAC risk, followed by an in-depth functional in-silico study using TCGA and ICGC data. We assessed whether CS-related genes were associated with prognosis at germline and somatic levels. We investigated the immune infiltration of PDAC tumors according to their transcriptomic profile.
Results
Genetic variation in FCN1 and PLAT was significantly associated with PDAC risk. PDAC patients with elevated expression of IGHG3 , IGKC , IGHM , F2R , F2RL2 , CFI , A2M , and C4A displayed improved survival and higher infiltration of CD8 + , B cells, and Th1 cells. Individuals with high expression levels of FGA , SERPINE1 , FGG , and F3 had poorer survival, higher infiltration of Tregs, and lower infiltration of CD8+ cells.
Conclusions
Results from this study suggest that CS-related genes play a role in PDAC genetic susceptibility and survival through specific immune cell infiltration.
