Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Dec 12;24(24):17398.
doi: 10.3390/ijms242417398.

Can CD133 Be Regarded as a Prognostic Biomarker in Oncology: Pros and Cons

Alisa Gisina  1 , Yan Kim  1 , Konstantin Yarygin  1 , Alexey Lupatov  1
Affiliations
Review

Can CD133 Be Regarded as a Prognostic Biomarker in Oncology: Pros and Cons

Alisa Gisina et al. Int J Mol Sci. .

Abstract

The CD133 cell membrane glycoprotein, also termed prominin-1, is expressed on some of the tumor cells of both solid and blood malignancies. The CD133-positive tumor cells were shown to exhibit higher proliferative activity, greater chemo- and radioresistance, and enhanced tumorigenicity compared to their CD133-negative counterparts. For this reason, CD133 is regarded as a potential prognostic biomarker in oncology. The CD133-positive cells are related to the cancer stem cell subpopulation in many types of cancer. Recent studies demonstrated the involvement of CD133 in the regulation of proliferation, autophagy, and apoptosis in cancer cells. There is also evidence of its participation in the epithelial-mesenchymal transition associated with tumor progression. For a number of malignant tumor types, high CD133 expression is associated with poor prognosis, and the prognostic significance of CD133 has been confirmed in a number of meta-analyses. However, some published papers suggest that CD133 has no prognostic significance or even demonstrate a certain correlation between high CD133 levels and a positive prognosis. This review summarizes and discusses the existing evidence for and against the prognostic significance of CD133 in cancer. We also consider possible reasons for conflicting findings from the studies of the clinical significance of CD133.

Keywords: CD133; cancer biomarker; cancer prognosis; cancer stem cells; prominin-1.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure and cellular localization of CD133. (A) Topological model of CD133 molecule at the plasma membrane. CD133 molecule has nine N-linked glycosylation sites [12]. (B) Subcellular localization of CD133. CD133 was detected in cell membrane; cytoplasm, including endoplasmic reticulum and Golgi apparatus; and nucleus. Created with BioRender.com.
Figure 2
Figure 2
Involvement of CD133 in the Wnt/β-catenin signaling in cancer cells. Wnt—wingless-related integration site; HDAC6—histone deacetylase 6. The first intracellular loop domain of CD133 is able to physically bind to HDAC6 and β-catenin forming a ternary complex ensuring β-catenin stabilization. Created with BioRender.com.
Figure 3
Figure 3
Involvement of CD133 in the PI3K/Akt signaling pathway in cancer cells. PI3K—phosphoinositide 3-kinase; Akt—RAC-alpha serine/threonine-protein kinase (a.k.a. protein kinase B alpha); MDM2—E3 ubiquitin-protein ligase Mdm2; p53—transformation-related protein 53; MKP-1—protein kinase phosphatase-1; MAPKs—mitogen-activated protein kinases; JNK—c-Jun-NH(2)-terminal kinase; BCL-2—B-cell lymphoma 2 protein, apoptosis regulator; BCL-XL—anti-apoptotic protein, BCL2 family member; MCL-1—apoptosis regulator, BCL2 family member. The C-terminal cytoplasmic domain of CD133 is able to physically bind to PI3K. Created with BioRender.com.
Figure 4
Figure 4
Some examples of commercial antibodies used to recognize different domains of CD133 molecule (based on review [84]). Created with BioRender.com.
Figure 5
Figure 5
Intra-tumoral and circulating CD133-positive cells in cancer patients (based on the results of glioma studies). Higher percentage of CD133-positive endothelial progenitors recruited from bone marrow for tumor neovascularization is associated with lower patient survival [189]. Perivascular niches enriched with CD133-positive cells are several times more numerous in the higher stage gliomas [145]. CD133-positive neural progenitors in glioblastomas may contribute to a more favorable course of cancer disease [187]. Created with BioRender.com.
See this image and copyright information in PMC

References

    1. Immervoll H., Hoem D., Sakariassen P.Ø., Steffensen O.J., Molven A. Expression of the “Stem Cell Marker” CD133 in Pancreas and Pancreatic Ductal Adenocarcinomas. BMC Cancer. 2008;8:48. doi: 10.1186/1471-2407-8-48. - DOI - PMC - PubMed
    1. Mak A.B., Pehar M., Nixon A.M.L., Williams R.A., Uetrecht A.C., Puglielli L., Moffat J. Post-Translational Regulation of CD133 by ATase1/ATase2-Mediated Lysine Acetylation. J. Mol. Biol. 2014;426:2175–2182. doi: 10.1016/j.jmb.2014.02.012. - DOI - PMC - PubMed
    1. Miraglia S., Godfrey W., Yin A.H., Atkins K., Warnke R., Holden J.T., Bray R.A., Waller E.K., Buck D.W. A Novel Five-Transmembrane Hematopoietic Stem Cell Antigen: Isolation, Characterization, and Molecular Cloning. Blood. 1997;90:5013–5021. doi: 10.1182/blood.V90.12.5013. - DOI - PubMed
    1. Yin A.H., Miraglia S., Zanjani E.D., Almeida-Porada G., Ogawa M., Leary A.G., Olweus J., Kearney J., Buck D.W. AC133, a Novel Marker for Human Hematopoietic Stem and Progenitor Cells. Blood. 1997;90:5002–5012. doi: 10.1182/blood.V90.12.5002. - DOI - PubMed
    1. Weigmann A., Corbeil D., Hellwig A., Huttner W.B. Prominin, a Novel Microvilli-Specific Polytopic Membrane Protein of the Apical Surface of Epithelial Cells, Is Targeted to Plasmalemmal Protrusions of Non-Epithelial Cells. Proc. Natl. Acad. Sci. USA. 1997;94:12425–12430. doi: 10.1073/pnas.94.23.12425. - DOI - PMC - PubMed