Expression of CD133 Cancer Stem Cell Marker in Melanoma: A Systematic Review and Meta-Analysis

Madjd, Zahra; Erfani, Elham; Gheytanchi, Elmira; Moradi‐Lakeh, Maziar; Shariftabrizi, Ahmad; Asadi‐Lari, Mohsen

doi:10.5301/jbm.5000209

Cited by 30 publications

(17 citation statements)

References 54 publications

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“…For example, a metaanalysis of 299 melanoma cases dedicated to the expression of CD133 by skin melanoma cells showed that only the presence of CD133 does not always indicate that the cell belongs to CSC, but a combination with ABCB5 expression gives a more accurate result. [22] As for the association of CSC with an increased degree of invasion and growth rate, in this case our results are absolutely consistent with other studies. [23] The relationship of the markers of CSC with metastasis and a long-term prognosis is also interesting, in the study published by Klein WM et all, it was shown that in the analysis of 84 cases of metastatic melanoma, in each case, expression of markers of CSC was found in metastasis, which again positively correlates with our results.…”

Section: Discussionsupporting

confidence: 93%

Prognostic Value of Tumor Stem Cells and Anaplastic Lymphoma Kinase Expression in Patients with Primary Cutaneous Melanoma

Сергеевич¹,

Mikhailovich²,

Anatolievna³

et al. 2019

JCTR

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Melanoma is the most aggressive cutaneous neoplasm. Cancer stem cells (CSCs) may be one of the reasons for the low sensitivity of melanoma to chemotherapy, the short curative effect and the development of resistance to the targeted therapy, as well as the lack of efficiency of immune checkpoint inhibitors and disease relapses. The aim of our the study was to determine the influence of the expression of stem cells markers (АВСВ5 и CD133) and tyrosine kinases of mutated Anaplastic Lymphoma Kinase (ALK) genes found in primary tumors on survival of patients with stage I-II cutaneous melanomas. Materials of 48 patients with melanoma were used, and their morphological parameters (tumor thickness, invasion level, lymphoid infiltration) were assessed. The expression of CSCs markers, mutant kinases was determined using the immunohistochemical method. The statistical significance of the influence of the parameters studied on the overall (OS) and 2year relapse-free (RFS) survival was assessed by calculating the correlation coefficient using the rank method. Stem cell markers were found in 25 (52%) of 48 patients with cutaneous melanomas. ABCB5 was expressed in 20 (54%), CD133 was expressed in 17 (46%) patients. The co-expression of both markers was observed in 12 patients (32%). The 2-year OS in the group with CSC markers expressed (first group) was 76%, whereas in the group w/o such markers expressed (second group), the OS was 91.31%. The rates of RFS also differed between the two groups: in the first, RFS was 80%, and in the second one, it reached 91.31%. CD133 marker was found in 80% of the first group patients with metastases and relapses. A strong correlation was found between the increase percentage of cells expressing CD133 and the increase invasion level. (P=0.879 ±0.107). A strong correlation was found between the increase percentage of cells expressing ABCB5 and the increase tumor thickness. (P=0.943 ±0.088). The expression of mutant ALK was found in 28% of patients with CSC markers detected, and no statistically significant correlation between the prognosis and the presence of ALK was found. ABCB5 and CD133+ are promising markers of tumor stem cells applicable to predicting the clinical course of primary cutaneous melanomas. A correlation between АВСВ5 and CD133 markers and a number of morphological parameters shows the importance of their study for understanding the fundamental mechanisms of melanoma carcinogenesis. The inhibition of ABCB5 and CD133+ markers and mutant ALK may serve as a target for the therapy for melanoma in perspective.

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Section: Discussionsupporting

confidence: 93%

Prognostic Value of Tumor Stem Cells and Anaplastic Lymphoma Kinase Expression in Patients with Primary Cutaneous Melanoma

Сергеевич¹,

Mikhailovich²,

Anatolievna³

et al. 2019

JCTR

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“…We first analyzed the stemness marker CD133 [25] protein expression by western blot in total cell lysates and found higher level in MSC as compared to PC-E and PC-L as shown in Figure 1A. We then investigated if, similar to colorectal cancer, CD133 expression level correlates with LD abundance [8].…”

Section: Resultsmentioning

confidence: 99%

Lipid Storage and Autophagy in Melanoma Cancer Cells

Giampietri

Petrungaro

Cordella

et al. 2017

IJMS

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Cancer stem cells (CSC) represent a key cellular subpopulation controlling biological features such as cancer progression in all cancer types. By using melanospheres established from human melanoma patients, we compared less differentiated melanosphere-derived CSC to differentiating melanosphere-derived cells. Increased lipid uptake was found in melanosphere-derived CSC vs. differentiating melanosphere-derived cells, paralleled by strong expression of lipogenic factors Sterol Regulatory Element-Binding Protein-1 (SREBP-1) and Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ). An inverse relation between lipid-storing phenotype and autophagy was also found, since microtubule-associated protein 1A/1B-Light Chain 3 (LC3) lipidation is reduced in melanosphere-derived CSC. To investigate upstream autophagy regulators, Phospho-AMP activated Protein Kinase (P-AMPK) and Phospho-mammalian Target of Rapamycin (P-mTOR) were analyzed; lower P-AMPK and higher P-mTOR expression in melanosphere-derived CSC were found, thus explaining, at least in part, their lower autophagic activity. In addition, co-localization of LC3-stained autophagosome spots and perilipin-stained lipid droplets was demonstrated mainly in differentiating melanosphere-derived cells, further supporting the role of autophagy in lipid droplets clearance. The present manuscript demonstrates an inverse relationship between lipid-storing phenotype and melanoma stem cells differentiation, providing novel indications involving autophagy in melanoma stem cells biology.

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“…We used relatively high xmrk expression levels to hallmark a dedifferentiation state of Xiphophorus melanoma cells. Melanoma stem cell makers and metastasis‐related genes prom1 (CD133), itga6, itgab, itgb1, tbx2 , zeb1 , cdh7 , cdh20, and cfl (Figure c; (Argaw‐Denboba et al., ; Bosserhoff, Ellmann, & Kuphal, ; Bracalente et al., ; Madjd et al., ; Moore et al., ; Zhao et al., ; Zimmerer et al., ) were found to be co‐expressed with xmrk . These observations show xmrk is associated with a cluster of genes that are capable of maintaining the cells in an undifferentiated state.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Xiphophorus and human melanoma transcriptomes reveals conserved pathway interactions

Boswell

et al. 2018

Pigment Cell Melanoma Res

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Comparative analysis of human and animal model melanomas can uncover conserved pathways and genetic changes that are relevant for the biology of cancer cells. Spontaneous melanoma in Xiphophorus interspecies backcross hybrid progeny may be informative in identifying genes and functional pathways that are similarly related to melanoma development in all vertebrates, including humans. To assess functional pathways involved in the Xiphophorus melanoma, we performed gene expression profiling of the melanomas produced in interspecies BC and successive backcross generations (i.e., BC ) of the cross: X. hellerii × [X. maculatus Jp 163 A × X. hellerii]. Using RNA-Seq, we identified genes that are transcriptionally co-expressed with the driver oncogene, xmrk. We determined functional pathways in the fish melanoma that are also present in human melanoma cohorts that may be related to dedifferentiation based on the expression levels of pigmentation genes. Shared pathways between human and Xiphophorus melanomas are related to inflammation, cell migration, cell proliferation, pigmentation, cancer development, and metastasis. Our results suggest xmrk co-expressed genes are associated with dedifferentiation and highlight these signaling pathways as playing important roles in melanomagenesis.

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Expression of CD133 Cancer Stem Cell Marker in Melanoma: A Systematic Review and Meta-Analysis

Abstract: Our findings suggest that CD133 is not yet proven to be an appropriate biomarker in identifying CSCs of melanoma. Thus, detection of CD133 in combination with other putative CSC markers may be more valuable for clinical application.

Cited by 30 publications

References 54 publications

Prognostic Value of Tumor Stem Cells and Anaplastic Lymphoma Kinase Expression in Patients with Primary Cutaneous Melanoma

Prognostic Value of Tumor Stem Cells and Anaplastic Lymphoma Kinase Expression in Patients with Primary Cutaneous Melanoma

Lipid Storage and Autophagy in Melanoma Cancer Cells

Comparison of Xiphophorus and human melanoma transcriptomes reveals conserved pathway interactions

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