The risk of pancreatic adenocarcinoma following SARS-CoV family infection

Amin Ebrahimi Sadrabadi,Alexander M Seifalian,Arsalan Jalili,Ahmad Bereimipour,Mazaher Gholipurmalekabadi,Behrouz Farhadihosseinabadi

doi:10.1038/s41598-021-92068-4

Abstract

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was “double-stranded RNA binding” and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.

Highlights

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world
Abbreviations angiotensin-converting enzyme 2 (ACE2) Angiotensin-converting enzyme 2 ADAR1 Adenosine deaminases acting on RNA 1 ARP2/3 Actin-related proteins-2/3 biological process (BP) Biological process CASP3 Caspase 3 CREB1 CAMP responsive element binding protein 1 differentially expressed genes (DEGs) Differentially expressed genes double stranded RNA binding domain (dsRBD) Double stranded RNA binding domain GEO Gene expression omnibus GEPIA Gene expression profiling interactive analysis
In March 2020, the World Health Organization (WHO) identified Covid-19 as a pandemic and called on governments around the world to manage the protection of the population against COVID-193,4

Summary

Introduction

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Viruses may induce genomic instability and alter the expression levels of vital cell-regulating molecules such as miRNAs. In SARS-COV-1 infection, changes in the quantity and quality of tumour suppressor proteins such as pRb have been reported. Loss of cell–cell contact inhibition occurs following SARS-CoV virus infection[8]. Oxidative stress is another mechanism that may lead to carcinogenesis after viral infections. Inflammatory response, cytokine storm, and oxidative stress are considered as the main cause of acute respiratory distress syndrome in patient with SARS-CoV virus infection. ROS can enhance cell invasion, proliferation, angiogenesis, cell survival, and even drug resistance by interacting with intracellular signalling pathways, indicating the possible role of these molecules in cancer development following viral infections[10]

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