In silico analysis identifies neuropilin-1 as a potential therapeutic target for SARS-Cov-2 infected lung cancer patients

Aging (Albany NY). 2021 Jun 24;13(12):15770-15784. doi: 10.18632/aging.203159. Epub 2021 Jun 24.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), and is highly contagious and pathogenic. TMPRSS2 and Neuropilin-1, the key components that facilitate SARS-CoV-2 infection, are potential targets for treatment of COVID-19. Here we performed a comprehensive analysis on NRP1 and TMPRSS2 in lung to provide information for treating comorbidity of COVID-19 with lung cancer. NRP1 is widely expressed across all the human tissues while TMPRSS2 is expressed in a restricted pattern. High level of NRP1 associates with worse prognosis in multiple cancers, while high level of TMPRSS2 is associated with better survival of Lung Adenocarcinoma (LUAD). Moreover, NRP1 positively correlates with the oncogenic Cancer Associated Fibroblast (CAF), macrophage and endothelial cells infiltration, negatively correlates with infiltration of CD8+ T cell, the tumor killer cell in Lung Squamous cell carcinoma (LUSC). TMPRSS2 shows negative correlation with the oncogenic events in LUAD. RNA-seq data show that NRP1 level is slightly decreased in peripheral blood of ICU admitted COVID-19 patients, unaltered in lung, while TMPRSS2 level is significantly decreased in lung of COVID-19 patients. Our analysis suggests NRP1 as a potential therapeutic target, while sets an alert on targeting TMPRSS2 for treating comorbidity of COVID-19 and lung cancers.

Keywords: COVID-19; NRP1; SARS-CoV-2; TMPRSS2; immune infiltration; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / mortality
  • CD8-Positive T-Lymphocytes / metabolism
  • COVID-19 / genetics
  • COVID-19 / metabolism
  • Cancer-Associated Fibroblasts / metabolism
  • Computer Simulation
  • Endothelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Macrophages / metabolism
  • Neuropilin-1 / genetics
  • Neuropilin-1 / physiology*
  • RNA-Seq
  • SARS-CoV-2
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*

Substances

  • NRP1 protein, human
  • Neuropilin-1
  • Serine Endopeptidases
  • TMPRSS2 protein, human