Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

Yang, Fang; Cao, Lulu; Sun, Zhixin; Jin, Juan; Fang, Hehui; Zhang, Wenwen; Guan, Xiaoxiang

doi:10.7150/ijbs.16874

Cited by 42 publications

(34 citation statements)

References 50 publications

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“…One large‐scale analysis of 1,127 patient samples showed no association between CD44 + /CD24 − and survival , whereas one report only showed poor outcomes in ER − patients exhibiting this phenotype, with a trend to showing better survival in ER‐positive patients . Further combination analyses reveal that CD44 + /CD24 − plus ALDH1A1, ALDH1A3, integrin α‐6, CD133, EpCAM, and Ki‐67 − produces mixed results , with different phenotypes being more or less prevalent in different types of tumors or stages.…”

Section: Clinical Impact Of Cscs: Literature Evidencementioning

confidence: 99%

The Clinical Impact of Cancer Stem Cells

2019

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Patients with cancer can go though many stages in their disease, including diagnosis, recurrence, metastasis, and treatment failure. Cancer stem cells (CSCs) are a subgroup of cells within tumors that may explain the mechanism by which tumors recur and progress. CSCs can both self-renew and produce progenitor cells of more differentiated cancer cells as well as heterogeneously demonstrate resistance and the abilities to migrate and metastasize. These "stemness" characteristics are often the result of dysregulation of one or more pathways, which can be detected by various biomarkers. Although there has been considerable laboratory research conducted on CSCs, its relevance to the practicing oncologist may seem questionable. We sought to determine the clinical impact of CSCs on patients. A systematic literature search was conducted to identify analyses containing survival information based on the expression of known CSC biomarkers in any cancer. Overall, 234 survival analyses were identified, of which 82% reported that high expression of CSC biomarker(s) resulted in poor overall survival and/or disease-free survival compared with low or no expression of the biomarker. Elevated stemness biomarker levels were also associated with decreased tumor differentiation, altered TNM stage, and increased metastasis. This analysis would suggest that CSCs have a clinical impact on patients and that practicing oncologists need to start considering incorporating CSC-targeting therapies into their patients' treatment regimens. The Oncologist 2020;25:123-131 Implications for Practice: Cancer stem cells (CSCs) may occur at any stage of cancer and are implicated in the occurrence of resistance, recurrence, and metastasis. A systematic literature analysis has shown that the presence of CSCs, identified via the upregulation of stemness pathway biomarkers, results in reduced survival across all cancers studied. Several CSCtargeting agents are currently approved, and several others are in clinical trials. Future treatment regimens will likely include CSC-targeting agents to enable the elimination of these holdouts to current therapies.

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Section: Clinical Impact Of Cscs: Literature Evidencementioning

confidence: 99%

The Clinical Impact of Cancer Stem Cells

2019

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“…Recently, the Hippo pathway, which controls the size of organs during development, has been linked to cancerous stem cells. 9,19,20 Matsubara, et al Reported the results of his research that inhibiting Hedgehog and mTOR will reduce the growth of CD133 + tumour cells on the L3.6pl cell line.41. Severe hypoxia is often found in breast cancer, so the levels of HIF-1α and HIF-2α proteins with immunohistochemical examination will increase compared to the normal surrounding tissue.…”

Section: Introductionmentioning

confidence: 99%

“…Breast cancer needs HIF-1α and HIF-2α for cell growth, and metastasis to lymph nodes and lungs, by inducing EMT breast cancer stem cells to make it easier for migration and invasion. [19][20][21][22][23][24] This study aimed to perceive the correlation of PD-L1 and CD133 expression with metastasis in invasive breast carcinoma of Luminal B subtype.…”

Section: Introductionmentioning

confidence: 99%

Correlation of PD-L1 and CD133 Expression with Metastasis in Invasive Breast Carcinoma of Luminal B Subtype

Anwar

Hernowo

Dewayani

et al. 2019

ijmsci

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Background: Breast carcinoma is a cancer with the highest number in women, Luminal B is the highest number of all types of invasive breast carcinoma in the world. Invasive breast carcinoma of luminal B is breast carcinoma with hormone-receptor positive (estrogen-receptor and/or progesterone-receptor positive), and either HER2 positive or HER2 negative with high levels of Ki-67. Determining the aggressiveness factor in invasive breast carcinoma is very important. PD-L1 is a checkpoint in the cancer cell immunity cycle that affects the aggressiveness of tumour cells and CD133 is a cancerous stem cell marker that plays a role in proliferation, renewal and invasion of tumour cells. This study aims to determine the relationship of PD-L1 and CD133 expression with metastasis in the invasive breast carcinoma of Luminal B subtype. Methods: This study was an observational analytic study with a case control design to analyze 40 cases of invasive breast carcinoma Luminal B subtype, then divided into 2 groups, metastasis and nonmetastasis groups of 20 cases respectively. Then, all samples were performed by PD-L1 and CD133 immunohistochemistry staining, and then were associated with metastasis. All data were analyzed statistically, tested with a value of p < 0.05 from a significant level then processed with SPSS 24.0 for Windows. Results: The results of this study indicate that there is a significant relationship in PD-L1 (p = 0.013), CD133 (p = 0.020) with metastasis. PD-L1 expression affects the incidence of metastasis more strongly than the CD133 expression, the high CD133 expression has the greatest risk of metastasis, compared to the high expression in PD-L1 (PD-L1 Odds Ratio : OR CD133 = 7.364 : 12,667). Conclusions: The more increase in expression of PD-L1 and CD133 which demonstrated the more tendency for metastasis shows that PD-L1 had the most influence on metastasis.

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“…BCSCs have been suggested to contribute to the increased aggressiveness and poor prognosis of TNBC. However, the high intratumor stemness heterogeneity reduces the prognostic and therapeutic value of the presence of tumor-initiating cells in this breast tumor subtype [ 28 ]. Among the stemness markers in TNBC, CD133 and EpCAM may be of interest since they have a direct relationship with malignancy of breast tumors.…”

Section: Discussionmentioning

confidence: 99%

Up-modulation of PLC-β2 reduces the number and malignancy of triple-negative breast tumor cells with a CD133+/EpCAM+ phenotype: a promising target for preventing progression of TNBC

et al. 2017

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Background: The malignant potential of triple negative breast cancer (TNBC) is also dependent on a sub-population of cells with a stem-like phenotype. Among the cancer stem cell markers, CD133 and EpCAM strongly correlate with breast tumor aggressiveness, suggesting that simultaneous targeting of the two surface antigens may be beneficial in treatment of TNBC. Since in TNBC-derived cells we demonstrated that PLC-β2 induces the conversion of CD133 high to CD133 low cells, here we explored its possible role in down-modulating the expression of both CD133 and EpCAM and, ultimately, in reducing the number of TNBC cells with a stem-like phenotype. Methods: A magnetic step-by-step cell isolation with antibodies directed against CD133 and/or EpCAM was performed on the TNBC-derived MDA-MB-231 cell line. In the same cell model, PLC-β2 was over-expressed or down-modulated and cell proliferation and invasion capability were evaluated by Real-time cell assays. The surface expression of CD133, EpCAM and CD44 in the different experimental conditions were measured by multi-color flow cytometry immunophenotyping. Results: A CD133

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Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

Cited by 42 publications

References 50 publications

The Clinical Impact of Cancer Stem Cells

The Clinical Impact of Cancer Stem Cells

Correlation of PD-L1 and CD133 Expression with Metastasis in Invasive Breast Carcinoma of Luminal B Subtype

Up-modulation of PLC-β2 reduces the number and malignancy of triple-negative breast tumor cells with a CD133+/EpCAM+ phenotype: a promising target for preventing progression of TNBC

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