Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer

Abstract

Purpose: CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC.Methods:CD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated.Results: High expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p<0.001).High CD133 expression was positively associated with proliferation biomarkers including p16, Cyclin E and Ki67 (p<0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3, and ITGA6. High expression of CD133 protein was associated with shorter BC specific survival (p=0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC specific survival (p=0.038). Conclusion:This study provides evidence for the prognostic value of CD133 in invasive BC.A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted. Research involving human participantsThis study was approved by the Nottingham Research Ethics Committee 2 (Reference title: Development of a molecular genetic classification of breast cancer). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Molecular characterization of lung cancer: A two‐miRNA prognostic signature based on cancer stem‐like cells related genes

“…At present, most studies have proved that CSCs are related to the recurrence, metastasis, and prognosis of tumors . Joseph et al found that the overexpression of CD133 as a surface marker of CSCs was positively correlated with proliferation of breast cancer cells, and negatively correlated with the patient's survival time. Bertolini found that CD133 + cell population in NSCLC was consistent with recurrence, metastasis, and high tumorigenicity.…”

“…Cancer stem cells (CSCs) is a new theory put forward in recent years, which provides new ideas and ways to explore the occurrence and development of tumors . Most studies show that CSCs, which have a strong ability of self‐replication and self‐renewal, can promote tumor growth, migration, and invasion . Many studies also find that CSCs are closely related to tumor recurrence, metastasis, and treatment resistance .…”

CD45dimCD34+CD38−CD133+ cells have the potential as leukemic stem cells in acute myeloid leukemia

“…CD133 has been reported to be a cancer stem cell marker in solid tumors [14,[32][33][34]. Several studies have shown that CD133 positive cells have the capacity for selfrenewal, differentiation, high proliferation, and forming tumors in xenografts [33,34].…”

Clinical significance of CD133 and Nestin in astrocytic tumor: The correlation with pathological grade and survival

“…CD133 and Nestin have also been studied regarding their impact on prognosis in a range of solid tumors. For instances, overexpression of CD133 confers poor prognosis in invasive breast cancer, colorectal cancer, pancreatic cancer, etc . In addition, the negative impact of Nestin on survival has also been observed in lung cancer, esophageal squamous cancer, bladder cancer, etc .…”

“…In addition, positive correlation was also observed between LGA, low-grade astrocytic tumors; HGA, high-grade astrocytic tumors cancer, colorectal cancer, pancreatic cancer, etc. [21][22][23] In addition, the negative impact of Nestin on survival has also been observed in lung cancer, esophageal squamous cancer, bladder cancer, etc. [24][25][26] Whereas in astrocytic tumor, the tumor of the central nervous system, the effects of CD133 and Nestin on prognosis are only discovered in a small volume of literatures.…”