CXC chemokines: Potential biomarker and immunotherapeutic target for uterine corpus endometrial carcinoma

PLoS One. 2024 Jan 17;19(1):e0277872. doi: 10.1371/journal.pone.0277872. eCollection 2024.

Abstract

Uterine corpus endometrial carcinoma (UCEC) is one of the most common type of gynecological malignancies. Multiple lines of evidence indicated that CXC chemokines exerted an anti-tumor immunological role in the tumor microenvironment which were critical regulators of cancer immunity. However, the relevance of CXC chemokines in the evaluation of prognosis and immune infiltration of UCEC remains to be explored. This study utilized various online databases, including TCGA, UALCAN, Kaplan-Meier Plotter, cBioPortal, TIMER2.0, TISIDB, and MethSurv to perform the analysis. Gene expression data from the TCGA-UCEC dataset indicated decreased expression of CXCL2/12 and increased expression of CXCL14/17. CXCL2/12 expression was negatively whereas CXCL14/17 expression was positively correlated with clinicopathological features of UCEC patients, including cancer stage, patients' age, weight and menopause status. Patients with higher CXCL12/14 expression corresponded with better clinical outcomes, which were not influenced by the genetic alterations. The differential expression of CXCL2/12/14/17 was not only significantly correlated with immune infiltration levels, but also the abundance of immune checkpoint inhibitors. Heatmaps of DNA methylation of CXCL2/12/14/17 were investigated, and 4 CpGs of CXCL2, 16 CpGs of CXCL12, 3 CpGs of CXCL14/17 were identified where altered methylation affected the prognosis of UCEC patients. These findings provided novel insights into the immunologic features of UCEC and might pave the way toward the prognostic evaluation and immunotherapy selection based on CXCL2/12/14/17 expression status.

MeSH terms

  • Biomarkers
  • Carcinoma, Endometrioid*
  • DNA Methylation
  • Databases, Factual
  • Endometrial Neoplasms* / genetics
  • Female
  • Humans
  • Immunotherapy
  • Tumor Microenvironment

Substances

  • Biomarkers

Grants and funding

This study was supported by the Natural Science Foundation of Liaoning Province (grant number: 2020-MS-253, 2019-BS-075).