Bioinformatic Analysis of the CXCR2 Ligands in Cancer Processes

Int J Mol Sci. 2023 Aug 27;24(17):13287. doi: 10.3390/ijms241713287.

Abstract

Human CXCR2 has seven ligands, i.e., CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8/IL-8-chemokines with nearly identical properties. However, no available study has compared the contribution of all CXCR2 ligands to cancer progression. That is why, in this study, we conducted a bioinformatic analysis using the GEPIA, UALCAN, and TIMER2.0 databases to investigate the role of CXCR2 ligands in 31 different types of cancer, including glioblastoma, melanoma, and colon, esophageal, gastric, kidney, liver, lung, ovarian, pancreatic, and prostate cancer. We focused on the differences in the regulation of expression (using the Tfsitescan and miRDB databases) and analyzed mutation types in CXCR2 ligand genes in cancers (using the cBioPortal). The data showed that the effect of CXCR2 ligands on prognosis depends on the type of cancer. CXCR2 ligands were associated with EMT, angiogenesis, recruiting neutrophils to the tumor microenvironment, and the count of M1 macrophages. The regulation of the expression of each CXCR2 ligand was different and, thus, each analyzed chemokine may have a different function in cancer processes. Our findings suggest that each type of cancer has a unique pattern of CXCR2 ligand involvement in cancer progression, with each ligand having a unique regulation of expression.

Keywords: CXCR2; Gro-α; IL-8; NF-κB; bioinformatics; chemokine; pan-cancer analysis.

MeSH terms

  • Chemokine CXCL1
  • Chemokines, CXC* / metabolism
  • Computational Biology
  • Glioblastoma*
  • Humans
  • Ligands
  • Male
  • Melanoma*
  • Prostatic Neoplasms*
  • Receptors, Interleukin-8B / metabolism
  • Tumor Microenvironment / genetics

Substances

  • Ligands
  • Receptors, Interleukin-8B
  • Chemokine CXCL1
  • Chemokines, CXC

Grants and funding

This study was supported by the statutory budget of the Department of Biochemistry and Medical Chemistry Pomeranian Medical University in Szczecin, Poland.