SIK2-positive tumor epithelial cells in breast cancer maybe potential anti-cancer messengers: A systematic analysis from a single-cell perspective

Environ Toxicol. 2024 Feb;39(2):768-782. doi: 10.1002/tox.23987. Epub 2023 Sep 29.

Abstract

Breast cancer is the most common malignancy in the world and one of the leading causes of cancer death, which is a heterogeneous disease involving genetic and environmental factors. Breast cancer stem cells (BCSCs) are the main players in the aggressiveness of different tumors, at the same time, these cells are the main challenge for cancer treatment. There are multiple treatment options for breast cancer (BC) patients and the lack of understanding of prognostic and predictive biomarkers for breast cancer is a potential research direction for us to develop better treatments in the future. In this paper, we conducted a correlation analysis between SIK2 and clinical traits by searching numerous BRCA datasets in the GEO database. The model was constructed and validated by incorporating tumor samples from the TCGA-BRCA cohort. Surprisingly, we found differential expression of SIK2 gene in individual tumor samples from the UCSC database. Subsequently, we found significantly high expression of SIK2 in epithelial cells by comparing the differential expression of SIK2 in different cell subpopulations and performed subsequent immune infiltration and pathway correlation analysis. Differential genes in SIK2+ epithelial cells, which may be potential therapeutic targets for breast cancer. In conclusion, our results suggest that SIK2 may be a potential prognostic and predictive biomarker that could serve as an oncogenic messenger for breast cancer. This discovery of SIK2 may provide more valuable references for potential therapeutic tools for breast cancer.

Keywords: SIK2; breast cancer; cancer suppressor gene; single-cell sequencing; tumor microenvironment.

MeSH terms

  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Mammary Neoplasms, Animal*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism

Substances

  • Protein Serine-Threonine Kinases
  • salt-inducible kinase-2, human