Effect of DPP4/CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives m62A and CD) regulations on patients with cancer and healthy individuals

Int J Oncol. 2023 Mar;62(3):41. doi: 10.3892/ijo.2023.5489. Epub 2023 Feb 17.


The worldwide COVID‑19 pandemic was brought on by a new coronavirus (SARS Cov‑2). A marker/receptor called Dipeptidyl peptidase 4/CD26(DPP4/CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 in COVID‑invaded cancer patients and its role on small molecule compounds remain unclear. The present study used the Human Protein Atlas, Monaco, and Schmiedel databases to analyze the expression of DPP4 in human tissues and immune cells. The association between DPP4 expression and survival in various tumor tissues was compared using GEPIA 2. The DNMIVD database was used to analyze the correlation between DPP4 expression and promoter methylation in various tumors. On the cBioPortal network, the frequency of DPP4 DNA mutations in various cancers was analyzed. The correlation between DPP4 expression and immunomodulators was analyzed by TISIDB database. The inhibitory effects of cordycepin (CD), N6, N6‑dimethyladenosine (m62A) and adenosine (AD) on DPP4 in cancer cells were evaluated. DPP4 was mainly expressed in endocrine tissue, followed by gastrointestinal tract, female tissue (mainly in placenta), male tissue (mainly in prostate and seminal vesicle), proximal digestive tract, kidney, bladder, liver, gallbladder and respiratory system. In immune cells, DPP4 mRNA was mainly expressed in T cells, and its expression was upregulated in esophageal carcinoma, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, stomach adenocarcinoma, thyroid carcinoma and thymoma. However, it was downregulated in breast invasive carcinoma, kidney chromophobe, lung squamous cell carcinoma and skin cutaneous melanoma. Thus, DPP4 is involved in viral invasion in most types of cancer. The expression of DPP4 could be inhibited by CD, m62A and AD in different tumor cells. Moreover, CD significantly inhibited the formation of GFP‑positive syncytial cells. In vivo experiments with AD injection further showed that AD significantly inhibited lymphocyte activating factor 3 expression. These drugs may have potential to treat COVID‑19 by targeting DPP4. Thus, DPP4 may be medically significant for SARS‑CoV‑2‑infected cancer patients, providing prospective novel targets and concepts for the creation of drugs against COVID‑19.

Keywords: COVID‑19; DPP4/CD26 gene; N6‑dimethyladenosine (m62A); adenosine; cancers; cordycepin; immune; susceptibility.

MeSH terms

  • Adenocarcinoma*
  • Adenosine
  • COVID-19* / genetics
  • Carcinoma, Hepatocellular*
  • Dipeptidyl Peptidase 4 / genetics
  • Dipeptidyl Peptidase 4 / metabolism
  • Female
  • Humans
  • Immunity
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Male
  • Melanoma*
  • Melanoma, Cutaneous Malignant
  • Pancreatic Neoplasms*
  • Pandemics
  • Prospective Studies
  • SARS-CoV-2
  • Skin Neoplasms*


  • Dipeptidyl Peptidase 4
  • cordycepin
  • Adenosine
  • DPP4 protein, human

Grants and funding

The present study was supported by the Foundation of Science and Technology Department of Sichuan Province (grant no. 2022NSFSC0737), the Joint Innovation Special Project of Science and Technology Plan of Sichuan Province (grant no. 2022YFS0623-C3), in part by the Research Foundation of Luzhou City (grant no. 2021-SYF-37) and the National Natural Science Foundation of China (grant nos. 81672887, 82073263).