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
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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.

Abstract Image

感染 COVID-19 会通过 PI3K-AKT 信号通路促进胰腺癌的进展
方法基于GEO数据库中COVID-19患者和胰腺癌(PC)患者的mRNA-Seq数据,采用支持向量机(SVM)、LASSO-Cox回归分析和随机森林树(RF)筛选出两种疾病的共同特征基因,并分别进一步研究其对PC的影响和功能特征。结果发现COL10A1/FAP/FN1蛋白是COVID-19和PC的共同特征基因,在两种疾病中均显著上调,对PC有良好的诊断效果。基于COL10A1/FAP/FN1的风险模型具有良好的PC风险预测能力和临床应用潜力。基于COL10A1/FAP/FN1表达水平的肿瘤分型有效地将PC分为不同的亚型,并在生存预后、免疫水平、免疫检查点表达水平、常见肿瘤突变位点的突变状态以及药物敏感性分析等方面显示出两种亚型之间的显著差异。结论 COVID-19 的特征基因 COL10A1/FAP/FN1 的表达上调是 PC 的潜在诊断靶点,而 FN1 的表达上调可能通过激活 PI3K-AKT 信号通路促进 PC 的进展。基于COL10A1/FAP/FN1的分型为PC提供了一种新的分型方法,也为PC的精细化治疗和后续临床研究提供了良好的参考和思路。
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