Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers
Quadruple-negative breast cancer (QNBC) lacks traditional actionable targets, including androgen receptor (AR). QNBC disproportionately afflicts and impacts patients of African genetic ancestry. Kinesin family member C1 (KIFC1/HSET), a centrosome clustering protein that prevents cancer cells from un...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/22/16072 |
| _version_ | 1797459029411233792 |
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| author | Nikita Jinna Yate-Ching Yuan Padmashree Rida |
| author_facet | Nikita Jinna Yate-Ching Yuan Padmashree Rida |
| author_sort | Nikita Jinna |
| collection | DOAJ |
| description | Quadruple-negative breast cancer (QNBC) lacks traditional actionable targets, including androgen receptor (AR). QNBC disproportionately afflicts and impacts patients of African genetic ancestry. Kinesin family member C1 (KIFC1/HSET), a centrosome clustering protein that prevents cancer cells from undergoing centrosome-amplification-induced apoptosis, has been reported to be upregulated in TNBCs and African-American (AA) TNBCs. Herein, we analyzed KIFC1 RNA levels and their associations with clinical features and outcomes among AR-low and AR-high TNBC tumors in three distinct publicly available gene expression datasets and in the breast cancer gene expression database (bc-GenExMiner). KIFC1 levels were significantly higher in AR-low and basal-like TNBCs than in AR-high and non-basal-like TNBCs, irrespective of the stage, grade, tumor size, and lymph node status. KIFC1 levels were also upregulated in AR-low tumors relative to AR-high tumors among Black and premenopausal women with TNBC. High KIFC1 levels conferred significantly shorter overall survival, disease-free survival, and distant metastasis-free survival among AR-low and basal-like TNBC patients in Kaplan–Meier analyses. In conclusion, KIFC1 levels may be upregulated in AR-low tumors and, specifically, in those of African descent, wherein it may promote poor outcomes. KIFC1 may be an actionable cancer-cell-specific target for the AR-low TNBC subpopulation and could aid in alleviating racial disparities in TNBC outcomes. |
| first_indexed | 2024-03-09T16:46:32Z |
| format | Article |
| id | doaj.art-020aa34ad02c4049b7c1cbb22dabe403 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:46:32Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-020aa34ad02c4049b7c1cbb22dabe4032023-11-24T14:45:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221607210.3390/ijms242216072Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast CancersNikita Jinna0Yate-Ching Yuan1Padmashree Rida2Department of Population Science, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USADepartment of Integrative Genomics and Bioinformatics, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USADepartment of Science, Rowland Hall, Salt Lake City, UT 84102, USAQuadruple-negative breast cancer (QNBC) lacks traditional actionable targets, including androgen receptor (AR). QNBC disproportionately afflicts and impacts patients of African genetic ancestry. Kinesin family member C1 (KIFC1/HSET), a centrosome clustering protein that prevents cancer cells from undergoing centrosome-amplification-induced apoptosis, has been reported to be upregulated in TNBCs and African-American (AA) TNBCs. Herein, we analyzed KIFC1 RNA levels and their associations with clinical features and outcomes among AR-low and AR-high TNBC tumors in three distinct publicly available gene expression datasets and in the breast cancer gene expression database (bc-GenExMiner). KIFC1 levels were significantly higher in AR-low and basal-like TNBCs than in AR-high and non-basal-like TNBCs, irrespective of the stage, grade, tumor size, and lymph node status. KIFC1 levels were also upregulated in AR-low tumors relative to AR-high tumors among Black and premenopausal women with TNBC. High KIFC1 levels conferred significantly shorter overall survival, disease-free survival, and distant metastasis-free survival among AR-low and basal-like TNBC patients in Kaplan–Meier analyses. In conclusion, KIFC1 levels may be upregulated in AR-low tumors and, specifically, in those of African descent, wherein it may promote poor outcomes. KIFC1 may be an actionable cancer-cell-specific target for the AR-low TNBC subpopulation and could aid in alleviating racial disparities in TNBC outcomes.https://www.mdpi.com/1422-0067/24/22/16072androgen receptorHsetkinesin family member C1quadruple-negative breast cancertriple-negative breast cancer |
| spellingShingle | Nikita Jinna Yate-Ching Yuan Padmashree Rida Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers International Journal of Molecular Sciences androgen receptor Hset kinesin family member C1 quadruple-negative breast cancer triple-negative breast cancer |
| title | Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers |
| title_full | Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers |
| title_fullStr | Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers |
| title_full_unstemmed | Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers |
| title_short | Kinesin Family Member C1 (KIFC1/HSET) Underlies Aggressive Disease in Androgen Receptor-Low and Basal-Like Triple-Negative Breast Cancers |
| title_sort | kinesin family member c1 kifc1 hset underlies aggressive disease in androgen receptor low and basal like triple negative breast cancers |
| topic | androgen receptor Hset kinesin family member C1 quadruple-negative breast cancer triple-negative breast cancer |
| url | https://www.mdpi.com/1422-0067/24/22/16072 |
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