Comprehensive analysis of the homeobox family genes in breast cancer demonstrates their similar roles in cancer and development

Abstract

Background

The homeobox (HOX) family consists of 39 genes whose expressions are tightly controlled and coordinated within the family, during development. We performed a comprehensive analysis of this gene family in cancer settings.

Methods

Gene correlation analysis was performed using breast cancer data available in The Cancer Genome Atlas (TCGA) and data from the patients admitted to our hospital. We also analyzed the data of normal breast tissue (GSE20437). We next collected gene expression and prognosis data of breast cancer patients (GSE11121, GSE7390, GSE3494, and GSE2990) and performed unsupervised hierarchal clustering by the HOX gene expression pattern and compared prognosis. We additionally performed this analysis to leukemia (available in TCGA) and sarcoma (GSE20196) data.

Results

Gene correlation analysis showed that the proximal HOX genes exhibit strong interactions and are expressed together in breast cancer, similar to the expression observed during development. However, in normal breast tissue, less interactions were observed. Breast cancer microarray meta-data classified by the HOX gene expression pattern predicted the prognosis of luminal B breast cancer patients (p = 0.016). Leukemia (p = 0.00016) and sarcoma (p = 0.018) presented similar results. The Wnt signaling pathway, one of the major upstream signals of HOX genes in development, was activated in the poor prognostic group. Interestingly, poor prognostic cancer presented stronger correlation in the gene family compared to favorable prognostic cancer.

Conclusion

Comprehensive analysis of the HOX family demonstrated their similar roles in cancer and development, and indicated that the strong interaction of HOX genes might be specific to malignancies, especially in the case of poor prognostic cancer.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors greatly thank Mr. Kazuya Takakuwa for help in bioinformatics analysis. They also thank Mr. Kazuhiro Miyao for scientific advice.

Funding

This work was supported by Japan Society for the Promotion of Science (Grant Number 19K23897).

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Correspondence to Tetsu Hayashida.

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Nakashoji, A., Hayashida, T., Yamaguchi, S. et al. Comprehensive analysis of the homeobox family genes in breast cancer demonstrates their similar roles in cancer and development. Breast Cancer Res Treat (2021). https://doi.org/10.1007/s10549-020-06087-2

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Keywords

  • Homeobox
  • Breast cancer
  • Correlation
  • Development
  • Embryogenesis
  • Wnt signaling