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Abstract
Background Patients with pancreatic ductal adenocarcinoma (PDAC) are at a higher infection risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have a worse outcome, but the underlying detailed reasons have not yet been elucidated.
Materials and Methods We performed a multicohort analysis Using sequencing data from bulk and single-cell RNA derived from tissue, blood, and nasopharyngeal samples from PDAC and COVID-19 patients.
Results We identified upregulations of the crosstalk genes (CTGs) EPSTI1, USP18, NUSAP1, ANP32E, and PSMC2 in both diseases. These CTGs are expressed mainly by proliferating CD4, CD8, and natural killer (NK) cells. USP18 and EPSTI1 are associated with impaired interferon (IFN) signalling in patients who died from SARS- CoV-2-infection, whereas surviving COVID-19 patients had higher IFN scores. Dysregulated IFN signalling also correlated with high susceptibility of PDAC patients to SARS-CoV-2 infection with high mortality. Based on the identified CTG signature and clinicopathological characteristics, we designed a nomogram and found that it predicts the overall survival of PDAC patients even more accurately than the conventional nomogram.
Conclusions Therefore, PDAC and COVID-19 share regulatory mechanisms, which together exacerbate the already weakened immune response in PDAC and worsen prognosis. The evaluation and therapeutic targeting of the identified gene signature could contribute to the success of personalized treatment of SARS-CoV-2-infected PDAC patients.
S.S. Han: None.
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