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KIF18A as a potential biomarker to distinguish different breast cancer subtypes based on receptor status

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Abstract

The inhibition of KIF18A selectively reduces the viability of chromosomally unstable cancers due to increased mitotic vulnerability. KIF18A expression was also reported to be upregulated and associated with tumor aggressiveness in certain cancer types including breast cancer. Here, I first showed that KIF18A mRNA expression is higher in triple-negative breast cancer (TNBC) than in non-TNBC. I also found that ER (estrogen receptor)-negative and PR (progesterone receptor)-negative breast cancer cells have higher KIF18A mRNA expression compared to ER-positive and PR-positive breast cancer cells, respectively. In contrast, HER2-positive breast tumors have higher KIF18A expression compared to HER2-negative breast tumors. In terms of PAM50 breast cancer subtypes, KIF18A transcript levels were found to be the highest in basal-like breast cancer, followed by HER2-enriched, luminal B, normal-like and luminal A. Besides, in non-TNBC, cells with high AR (androgen receptor) mRNA expression have higher KIF18A mRNA expression than cells with low AR mRNA expression. Both non-TNBC and TNBC cells with high BRCA1 and BRCA2 mRNA expression levels were observed to have higher KIF18A mRNA expression than those with low BRCA1 and BRCA2 mRNA expression levels, respectively. Combined, this study demonstrates that breast tumors with low and high expression of ER, PR, HER2, AR and BRCA1/2 have differential transcript levels of KIF18A, pointing that KIF18A might contribute to the molecular differences between different breast cancer subtypes.

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Data used in the present study is publicly available, for which resources were given in the Methods section.

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  1. Department of Molecular Biology and Genetics, Tokat Gaziosmanpasa University, Tokat, Turkey

    Caglar Berkel

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Supplementary Information

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42764_2024_126_MOESM1_ESM.pdf

Supplementary Figure 1. Kaplan-Meier curves showing overall survival (OS) for breast cancer patients with low and high expression of KIF18A. Left: all subtypes combined. Right: HER2-negative. HR: Hazard ratio. Data from [Győrffy, 2021] (PDF 971 KB)

42764_2024_126_MOESM2_ESM.pdf

Supplementary Figure 2 KIF18A mRNA expression levels based on ER-, PR- and HER2 status analysed using data from another dataset to validate findings from TCGA dataset. Data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), accessed via https://www.mercuriolab.umassmed.edu/metabric [Curtis et al., 2012] (PDF 3930 KB)

42764_2024_126_MOESM3_ESM.pdf

Supplementary Figure 3 KIF18A mRNA and protein levels from cell lines based on breast cancer subtypes and BRCA1/2 mutation status. Data analysed using Dependency Map (DepMap) portal (https://depmap.org/portal/interactive/) (PDF 219 KB)

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Berkel, C. KIF18A as a potential biomarker to distinguish different breast cancer subtypes based on receptor status. GENOME INSTAB. DIS. 5, 89–96 (2024). https://doi.org/10.1007/s42764-024-00126-8

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