The Clinicopathological Significance of the CXCR2 Ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8 in Gastric Cancer

Anticancer Res. 2019 Dec;39(12):6645-6652. doi: 10.21873/anticanres.13879.

Abstract

Background/aim: We have previously reported that chemokine (C-X-C motif) receptor 2 (CXCR2) signaling was associated with the malignant progression of gastric cancer (GC). We thus examined the clinicopathological significance of CXCR2 ligands, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8, in GC.

Patients and methods: The expression of CXCR2 ligands in 590 GC cases was investigated by immunohistochemistry.

Results: The expression was as follows: CXCL1, 46.2% (257/557); CXCL2, 20.7% (122/590); CXCL3, 17.1% (101/589); CXCL5/CXCL6, 2.9% (17/589); CXCL7, 36.4% (215/590); and CXCL8 1.7% (10/585) of the cases. High invasion depth was correlated with CXCL1 expression. Lymph node metastasis and peritoneal cytology positivity were correlated with high expression of CXCL1 and CXCL7. The prognoses of the CXCL1-positive patients were significantly poorer than those of the CXCL1-negative patients (p<0.001).

Conclusion: Among the CXCR2 ligands, CXCL7 and especially CXCL1, might play an important role in the malignant progression of GC via CXCR2 signaling.

Keywords: CXCL1; CXCL7; CXCR2 ligands; gastric cancer; tumor microenvironment.

MeSH terms

  • Aged
  • Analysis of Variance
  • Chemokine CXCL1 / metabolism
  • Chemokine CXCL2 / metabolism
  • Chemokine CXCL5 / metabolism
  • Chemokine CXCL6 / metabolism
  • Chemokines, CXC / metabolism
  • Disease Progression
  • Female
  • Humans
  • Interleukin-8 / metabolism
  • Ligands
  • Lymphatic Metastasis
  • Male
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Receptors, Interleukin-8B / metabolism*
  • Retrospective Studies
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • beta-Thromboglobulin / metabolism

Substances

  • CXCL1 protein, human
  • CXCL2 protein, human
  • CXCL3 protein, human
  • CXCL5 protein, human
  • CXCL6 protein, human
  • CXCL8 protein, human
  • CXCR2 protein, human
  • Chemokine CXCL1
  • Chemokine CXCL2
  • Chemokine CXCL5
  • Chemokine CXCL6
  • Chemokines, CXC
  • Interleukin-8
  • Ligands
  • Neoplasm Proteins
  • PPBP protein, human
  • Receptors, Interleukin-8B
  • beta-Thromboglobulin