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PMID: 36077742 Published · epublish English Journal Article

Identification of EZH2 as Cancer Stem Cell Marker in Clear Cell Renal Cell Carcinoma and the Anti-Tumor Effect of Epigallocatechin-3-Gallate (EGCG).

Cancers ·Vol. 14 ·No. 17 ·2022-08-30

Lyu C, Wang L, Stadlbauer B, Noessner E, Buchner A, Pohla H

Abstract

The aim of the study was to develop a new therapeutic strategy to target cancer stem cells (CSCs) in clear cell renal cell carcinoma (ccRCC) and to identify typical CSC markers to improve therapy effectiveness. It was found that the corrected-mRNA expression-based stemness index was upregulated in kidney renal clear cell carcinoma (KIRC) tissues compared to non-tumor tissue and increased with higher tumor stage and grade. EZH2 was identified as a CSC marker and prognosis factor for KIRC patients. The expression of EZH2 was associated with several activated tumor-infiltrating immune cells. High expression of EZH2 was enriched in immune-related pathways, low expression was related to several metabolic pathways. Epigallocatechin-3-gallate (EGCG) was identified as the most potent suppressor of EZH2, was able to inhibit viability, migration, and invasion, and to increase the apoptosis rate of ccRCC CSCs. KIF11, VEGF, and MMP2 were identified as predictive EGCG target genes, suggesting a potential mechanism of how EZH2 might regulate invasiveness and migration. The percentages of FoxP3+ Treg cells in the peripheral blood mononuclear cells of ccRCC patients decreased significantly when cultured with spheres pretreated with EGCG plus sunitinib compared to spheres without treatment. Our findings provide new insights into the treatment options of ccRCC based on targeting CSCs.

Keywords
cancer stem cells kidney renal clear cell carcinoma phytochemicals prognosis tumor microenvironment
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lyu Chen
Tumor Immunology Laboratory, LIFE Center, LMU Klinikum, University Munich, D-82152 Planegg, Germany.
Wang Lili
Tumor Immunology Laboratory, LIFE Center, LMU Klinikum, University Munich, D-82152 Planegg, Germany. | Department of Radiology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310030, China.
Stadlbauer Birgit
Tumor Immunology Laboratory, LIFE Center, LMU Klinikum, University Munich, D-82152 Planegg, Germany. | Department of Urology, LMU Klinikum, University Munich, D-81377 Munich, Germany.
Noessner Elfriede ORCID
Immunoanalytics Research Group Tissue Control of Immunocytes, Helmholtz Zentrum München, D-81377 Munich, Germany.
Buchner Alexander ORCID
Tumor Immunology Laboratory, LIFE Center, LMU Klinikum, University Munich, D-82152 Planegg, Germany. | Department of Urology, LMU Klinikum, University Munich, D-81377 Munich, Germany.
Pohla Heike
Tumor Immunology Laboratory, LIFE Center, LMU Klinikum, University Munich, D-82152 Planegg, Germany. | Department of Urology, LMU Klinikum, University Munich, D-81377 Munich, Germany.
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Article Info
Journal
Cancers
Abbr.
Cancers (Basel)
ISSN
2072-6694
DOI
10.3390/cancers14174200
Published
2022-08-30
Epub
2022-00-30
Language
English
Region
Switzerland
NLM ID
101526829
PMCID
PMC9454898
Grants
China Scholarship Council · CSC No. 201908080121
External Links
PubMed source DOI: 10.3390/cancers14174200 PMC Full Text View journal details
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