Exploring CCL11 in breast cancer: unraveling its anticancer potential and immune modulatory effects involving the Akt-S6 signaling

J Cancer Res Clin Oncol. 2024 Feb 2;150(2):69. doi: 10.1007/s00432-023-05600-6.

Abstract

Background: CCL11, a chemokine known for recruiting immune cells to the tumor microenvironment (TME), has an unclear role in the context of its expression, patient prognosis, and the presence of tumor-infiltrating immune cells (TILs) in breast cancer.

Methods: The expression of CCL11 in invasive breast cancer (BRCA) was analyzed using TCGA database. Survival curve and Cox regression analysis determined the potential of CCL11 as an independent prognostic indicator. GSEA performed functional analysis on genes related to CCL11. CIBERSORT algorithm quantified the infiltration level of immune cells with varying CCL11 expression. Lastly, the correlation between CCL11 expression and anticancer drug sensitivity was examined. Immunohistochemistry (IHC) and qRT-PCR confirmed CCL11 expression in clinical tissue samples. The anti-tumor efficacy of CCL11 was investigated using CCK-8, plate formation, transwell assay, and Western blot.

Results: CCL11 expression was elevated in BRCA tumor tissues compared to adjacent normal tissues. Recurrence-free survival (RFS) was longer in patients with high expression of CCL11. Enrichment and co-expression analyses revealed CCL11's association with numerous immune-related signaling pathways and genes. Validation studies confirmed high CCL11 expression in breast cancer tissues. In vitro experiments substantiated CCL11's anticancer effects in BRCA.

Conclusion: CCL11 expression correlates with immune cell infiltration in breast cancer, indicating its potential as a prognostic biomarker for BRCA.

Keywords: Biomarker; Breast cancer; CCL11; Immune infiltration; Tumor microenvironment.

MeSH terms

  • Algorithms
  • Blotting, Western
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Chemokine CCL11
  • Female
  • Humans
  • Prognosis
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • Proto-Oncogene Proteins c-akt
  • CCL11 protein, human
  • Chemokine CCL11