Are embryonic stem cell markers and ALDH1A1 relevant in the context of breast cancer estrogen positivity?

Noha A Mousa, Amal Hussein, Noha M Elemam, Ghada Mohammed, Mona Elwany, Tasneem Basha, Amal A AlHammadi, Rana S Majzob, Iman M Talaat

Cancer medicine 2024 Feb

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Embryonic pluripotency markers are recognized for their role in ER- BC aggressiveness, but their significance in ER+ BC remains unclear. This study aims to investigate the prevalence of expression of pluripotency markers in ER+ BC and their effect on survival and prognostic indicators. We analyzed data of ER+ BC patients from three large cancer datasets to assess the expression of three pluripotency markers (NANOG, SOX-2, and OCT4), and the stem cell marker ALDH1A1. Additionally, we investigated associations between gene expression, through mRNA-Seq analysis, and overall survival (OS). The prevalence of mutational variants within these genes was explored. Using immunohistochemistry (IHC), we examined the expression and associations with clinicopathologic prognostic indicators of the four markers in 81 ER+ BC patients. Through computational analysis, NANOG and ALDH1A1 genes were significantly upregulated in ER+ BC compared to ER- BC patients (p < 0.001), while POU5F1 (OCT4) was downregulated (p < 0.001). NANOG showed an adverse impact on OS whereas ALDH1A1 was associated with a highly significant improved survival in ER+ BC (p = 4.7e-6), except for the PR- and HER2+ subgroups. Copy number alterations (CNAs) ranged from 0.4% to 1.6% in these genes, with the highest rate detected in SOX2. In the IHC study, approximately one-third of tumors showed moderate to strong expression of each of the four markers, with 2-4 markers strongly co-expressed in 56.8% of cases. OCT-4 and ALDH1A1 showed a significant association with a high KI-67 index (p = 0.009 and 0.008, respectively), while SOX2 showed a significant association with perinodal fat invasion (p = 0.017). Pluripotency markers and ALDH1A1 are substantially expressed in ER+ BC tumors with different, yet significant, associations with prognostic and survival outcomes. This study suggests these markers as targets for prospective clinical validation studies of their prognostic value and their possible therapeutic roles. © 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Citation

Noha A Mousa, Amal Hussein, Noha M Elemam, Ghada Mohammed, Mona Elwany, Tasneem Basha, Amal A AlHammadi, Rana S Majzob, Iman M Talaat. Are embryonic stem cell markers and ALDH1A1 relevant in the context of breast cancer estrogen positivity? Cancer medicine. 2024 Feb;13(3):e7004