Infection with COVID-19 promotes the progression of pancreatic cancer through the PI3K-AKT signaling pathway

Xusheng Zhang; Bendong Chen; Kejun Liu; Yongxin Ma; Yimin Liu; Hongcai Zhou; Peng Wei

doi:10.1007/s12672-023-00842-9

Infection with COVID-19 promotes the progression of pancreatic cancer through the PI3K-AKT signaling pathway

Discov Oncol. 2023 Dec 8;14(1):225. doi: 10.1007/s12672-023-00842-9.

Authors

Xusheng Zhang¹, Bendong Chen^{2

3}, Kejun Liu^{1

4}, Yongxin Ma¹, Yimin Liu¹, Hongcai Zhou¹, Peng Wei¹

Affiliations

¹ Ningxia Medical University, Yinchuan, 750004, China.
² Ningxia Medical University, Yinchuan, 750004, China. chenbendong@nxmu.edu.cn.
³ General Hospital of Ningxia Medical University, Yinchuan, 750004, China. chenbendong@nxmu.edu.cn.
⁴ General Hospital of Ningxia Medical University, Yinchuan, 750004, China.

Abstract

Objective: To investigate the effect of COVID-19 infection on pancreatic cancer.

Methods: Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used a support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. The above procedures were performed in R software.

Results: The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis.

Conclusion: The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promote the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, and also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

Keywords: COVID-19; Machine learning; PI3K-AKT signaling pathway; Pancreatic cancer; Random forest tree; Support vector machine.