CD133 expression may be useful as a prognostic indicator in colorectal cancer, a tool for optimizing therapy and supportive evidence for the cancer stem cell hypothesis: a meta-analysis

Zhao, Yang; Peng, Jing; Zhang, Enlong; Jiang, Ning; Jiang, Li; Zhang, Qi; Zhang, Xuening; Niu, Yuanjie

doi:10.18632/oncotarget.7054

Cited by 33 publications

(26 citation statements)

References 82 publications

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“…Selected EGFR‐positive cancer‐derived tumorspheres were investigated to identify driver genes for mediating PD‐L1 expression. Cancer stem cells (CSCs) exhibit high self‐renewal and pluripotency, thereby contributing to tumor recurrence . Moreover, CSCs have high drug resistance and antiapoptotic properties, which potentially enable them to survive clinical chemotherapies.…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor induces STAT1 expression to exacerbate the IFNr‐mediated PD‐L1 axis in epidermal growth factor receptor‐positive cancers

Cheng¹,

Lin

Tsai³

et al. 2018

Molecular Carcinogenesis

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The epidermal growth factor (EGF) receptor (EGFR) overexpressed in many cancers, including lung and head and neck cancers, and is involved in cancer cell progression and survival. PD-L1, increases in tumor cells to evade and inhibit CD8+ T cells, is a clinical immunotherapeutic target. This study investigated the molecular mechanism of EGF on regulating PD-L1 in EGFR-positive cancers and determined potential agents to reduce PD-L1 expression. RNA sequencing (RNAseq) and bioinformatics analysis were performed to determine potential driver genes that regulate PD-L1 in tumor cells-derived tumorspheres which mimicking cancer stem cells. Then, the specific inhibitors targeting EGFR were applied to reduce the expression of PD-L1 in vitro and in vivo. We validated that EGF could induce PD-L1 expression in the selected EGFR-positive cancers. RNAseq results revealed that STAT1 increased as a driver gene in KOSC-3-derived tumorspheres; these data were analyzed using PANTHER followed by NetworkAnalyst. The blockade of EGFR by afatinib resulted in decreased STAT1 and IRF-1 levels, both are transcriptional factors of PD-L1, and disabled the IFNr-STAT1-mediated PD-L1 axis in vitro and in vivo. Moreover, STAT1 knockdown significantly reduced EGF-mediated PD-L1 expression, and ruxolitinib, a JAK1/JAK2 inhibitor, significantly inhibited STAT1 phosphorylation to reduce the IFNr-mediated PD-L1 axis. These results indicate that EGF exacerbates PD-L1 by increasing the protein levels of STAT1 to enforce the IFNr-JAK1/2-mediated signaling axis in selected EGFR-positive cancers. The inhibition of EGFR by afatinib significantly reduced PD-L1 and may be a potential strategy for enhancing immunotherapeutic efficacy.

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Section: Introductionmentioning

confidence: 99%

Epidermal growth factor induces STAT1 expression to exacerbate the IFNr‐mediated PD‐L1 axis in epidermal growth factor receptor‐positive cancers

Cheng¹,

Lin

Tsai³

et al. 2018

Molecular Carcinogenesis

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“…CXCR4, a chemokine receptor, is expressed both in normal tissue stem cells of the breast, lung, and prostate gland, as well as tumors formed in those organs [ 29 – 32 ] Consistent with a role of colon TIC’s, colon cancer micrometastases require CXCR4 to initiate proliferation, and CXCR4/CD133 dual positive cells demonstrate enhanced tumorigenic capabilities over unsorted cells [ 33 , 34 ]. CXCR4 is also found to be overexpressed in the majority of colon cancer cases [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

An intestinal stem cell niche in Apc mutated neoplasia targetable by CtBP inhibition

et al. 2018

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C-terminal binding protein 2 (CtBP2) drives intestinal polyposis in the Apc min mouse model of human Familial Adenomatous Polyposis. As CtBP2 is targetable by an inhibitor of its dehydrogenase domain, understanding CtBP2’s role in adenoma formation is necessary to optimize CtBP-targeted therapies in Apc mutated human neoplasia. Tumor initiating cell (TIC) populations were substantially decreased in Apc min Ctbp2+/- intestinal epithelia. Moreover, normally nuclear Ctbp2 was mislocalized to the cytoplasm of intestinal crypt stem cells in Ctbp2+/- mice, both Apc min and wildtype, correlating with low/absent CD133 expression in those cells, and possibly explaining the lower burden of polyps in Apc min Ctbp2+/- mice. The CtBP inhibitor 4-chloro-hydroxyimino phenylpyruvate (4-Cl-HIPP) also robustly downregulated TIC populations and significantly decreased intestinal polyposis in Apc min mice. We have therefore demonstrated a critical link between polyposis, intestinal TIC’s and Ctbp2 gene dosage or activity, supporting continued efforts targeting CtBP in the treatment or prevention of Apc mutated neoplasia.

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“…Two meta-analyses have shown that higher CD133 levels are significantly associated with lymph node metastasis, clinical stage, and histopathological grade in colorectal cancer and esophageal carcinoma patients [17, 18]. …”

Section: Introductionmentioning

confidence: 99%

The effects of the location of cancer stem cell marker CD133 on the prognosis of hepatocellular carcinoma patients

et al. 2017

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BackgroundCD133 (prominin-1) is widely believed to be a cancer stem cell marker in various solid tumor types, and CD133 has been correlated with tumor-initiating capacity. Recently, the nuclear location of CD133 expression in tumors has been discussed, but hepatocellular carcinoma (HCC) has not been included in these discussions. The goal of this study was to investigate the location of CD133 expression in HCC and this location’s potential value as a prognostic indicator of survival in patients with HCC.MethodsWe enrolled 119 cancerous tissues and pair-matched adjacent normal liver tissue from HCC patients. These tissues were obtained immediately after operation, and tissue microarrays were subsequently constructed. The expression of CD133 was measured by immunohistochemistry (IHC), and the correlations between this expression and clinical characteristics and prognosis was estimated using statistical analysis.ResultsThe results showed that the CD133 protein expression levels of HCC in both the cytoplasm and nucleus were significantly higher than adjacent normal liver tissue. Kaplan–Meier survival and Cox regression analyses revealed that high CD133 expression in the cytoplasm was an independent predictor of poor prognosis for the overall survival (OS) and relapse-free survival (RFS) rates of HCC patients (P = 0.028 and P = 0.046, respectively). Surprisingly, high nuclear CD133 expression of HCC was an independent predictor of the good prognosis of the OS and RFS rates of HCC patients (P = 0.023 and P = 0.012, respectively).ConclusionsThe clinical evidence that revealed cytoplasmic CD133 expression was correlated with poor prognosis, while nuclear CD133 expression was significantly correlated with favorable prognosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3460-9) contains supplementary material, which is available to authorized users.

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CD133 expression may be useful as a prognostic indicator in colorectal cancer, a tool for optimizing therapy and supportive evidence for the cancer stem cell hypothesis: a meta-analysis

Cited by 33 publications

References 82 publications

Epidermal growth factor induces STAT1 expression to exacerbate the IFNr‐mediated PD‐L1 axis in epidermal growth factor receptor‐positive cancers

Epidermal growth factor induces STAT1 expression to exacerbate the IFNr‐mediated PD‐L1 axis in epidermal growth factor receptor‐positive cancers

An intestinal stem cell niche in Apc mutated neoplasia targetable by CtBP inhibition

The effects of the location of cancer stem cell marker CD133 on the prognosis of hepatocellular carcinoma patients

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