Cancer stem/progenitor signatures refine the classification of clear cell renal cell carcinoma with stratified prognosis and decreased immunotherapy efficacy

Zhou, Peng; Hu, Henglong; Lu, Yuchao; Xiao, Jun; Wang, Yanan; Yang, Xiufen; Xu, Jin‐Zhou; Liu, Chenqian; Wang, Shaogang; Hu, Jia

doi:10.1016/j.omto.2022.10.005

Cited by 3 publications

(5 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonsynonymous mutations of a single gene were extracted from the Mutect file and defined with reference to Brau et al ( 27 ). The methylation data were preprocessed with reference to the published report ( 29 ). The gene promoter region was defined as TSS1500, TSS200, 5’-UTR, and 1stExon.…”

Section: Methodsmentioning

confidence: 99%

Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma

Li,

Du,

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

BackgroundAlthough lactate metabolism-related genes (LMRGs) have attracted attention for their effects on cancer immunity, little is known about their function in clear cell renal cell carcinoma (ccRCC). The aim of this study was to examine the cellular specificity of lactate metabolism and how it affected the first-line treatment outcomes in ccRCC.MethodsGSE159115 was used to examine the features of lactate metabolism at the single-cell level. Utilizing the transcriptome, methylation profile, and genomic data from TCGA-KIRC, a multi-omics study of LMRG expression characteristics was performed. A prognostic index based on a gene-pair algorithm was created to assess how LMRGs affected patients’ clinical outcomes. To simulate the relationship between the prognostic index and the frontline treatment, pRRophetic and Subclass Mapping were used. E-MTAB-1980, E-MTAB-3267, Checkmate, and Javelin-101 were used for external validation.ResultsThe variable expression of some LMRGs in ccRCC can be linked to variations in DNA copy number or promoter methylation levels. Lactate metabolism was active in tumor cells and vSMCs, and LDHA, MCT1, and MCT4 were substantially expressed in tumor cells, according to single-cell analysis. The high-risk patients would benefit from immune checkpoint blockade monotherapy (ICB) and ICB plus tyrosine kinase inhibitors (TKI) therapy, whereas the low-risk individuals responded to mTOR-targeted therapy.ConclusionsAt the single-cell level, our investigation demonstrated the cellular specificity of lactate metabolism in ccRCC. We proposed that the lactate-related gene pair index might be utilized to identify frontline therapy responders in ccRCC patients as well as predict prognosis.

show abstract

Section: Methodsmentioning

confidence: 99%

Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma

Li,

Du,

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…While transiently activated in normal stem cells, they may encourage a long-lasting activation state in cancer stem cells [28]. CSCs are thought to be the main cause of recurrence and resistance to therapy and appear inherently resistant to chemo-and radiotherapy [29,30]. By promoting their active efflux, multidrug resistance (MDR) transporters (such as ATP-binding cassette-ABC) prevent drug accumulation in CSCs.…”

Section: Cancer Stem Cells: Definition and Propertiesmentioning

confidence: 99%

“…Zhou et al [29] clustered ccRCCs specimens into three subgroups based on stem/progenitor signatures. Significant antitumor immune infiltration (M1 macrophages, activated dendritic cells and CD4/CD8 T cells), enhanced HLA-I molecule expression, and cytolytic activity was associated with increased stemness signature.…”

Section: Renal Cancer Stem Cellsmentioning

confidence: 99%

“…In contrast, high-stemness subgroup showed increased immune checkpoint molecules, cancer-associated fibroblasts (CAFs), MDSCs, and regulatory T cells (Tregs) with robust immunosuppressive properties. In this scenario, these authors even hypothesized that a stemness-related gene signature may be useful to predict anti-PD-1 responses [29]. Over time, different agents have been assessed to target RCC CSCs.…”

Section: Renal Cancer Stem Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Cancer Stem Cells in Renal Cell Carcinoma: Origins and Biomarkers

Lasorsa,

Rutigliano,

Milella

et al. 2023

IJMS

View full text Add to dashboard Cite

The term “cancer stem cell” (CSC) refers to a cancer cell with the following features: clonogenic ability, the expression of stem cell markers, differentiation into cells of different lineages, growth in nonadhesive spheroids, and the in vivo ability to generate serially transplantable tumors that reflect the heterogeneity of primary cancers (tumorigenicity). According to this model, CSCs may arise from normal stem cells, progenitor cells, and/or differentiated cells because of striking genetic/epigenetic mutations or from the fusion of tissue-specific stem cells with circulating bone marrow stem cells (BMSCs). CSCs use signaling pathways similar to those controlling cell fate during early embryogenesis (Notch, Wnt, Hedgehog, bone morphogenetic proteins (BMPs), fibroblast growth factors, leukemia inhibitory factor, and transforming growth factor-β). Recent studies identified a subpopulation of CD133+/CD24+ cells from ccRCC specimens that displayed self-renewal ability and clonogenic multipotency. The development of agents targeting CSC signaling-specific pathways and not only surface proteins may ultimately become of utmost importance for patients with RCC.

show abstract

“…Over recent years, it has been proposed that the stem cell population isolated from the ccRCCs may be important in driving tumorigenesis and resistance to therapy [40]. Traditional cancer treatments like chemotherapy and radiotherapy remove most of the tumour cells from the bulk of the tumour; however, the CSC pool escapes from being eliminated [41,42].…”

Section: Effect Of Csc Markers Cd105 Cd44 and Cd133 In Ccrcc Progress...mentioning

confidence: 99%

In Vitro and In Silico Analysis of Epithelial-Mesenchymal Transition and Cancer Stemness as Prognostic Markers of Clear Cell Renal Cell Carcinoma

Sharma

Balta

Raza

et al. 2023

Cancers

View full text Add to dashboard Cite

The process of epithelial-mesenchymal transition (EMT) involves the phenotypic transformation of cells from epithelial to mesenchymal status. The cells exhibiting EMT contain features of cancer stem cells (CSC), and the dual processes are responsible for progressive cancers. Activation of hypoxia-inducible factors (HIF) is fundamental to the pathogenesis of clear cell renal cell carcinoma (ccRCC), and their role in promoting EMT and CSCs is crucial for ccRCC tumour cell survival, disease progression, and metastatic spread. In this study, we explored the status of HIF genes and their downstream targets, EMT and CSC markers, by immunohistochemistry on in-house accrued ccRCC biopsies and adjacent non-tumorous tissues from patients undergoing partial or radical nephrectomy. In combination, we comprehensively analysed the expression of HIF genes and its downstream EMT and CSC-associated targets relevant to ccRCC by using publicly available datasets, the cancer genome atlas (TCGA) and the clinical proteome tumour analysis consortium (CPTAC). The aim was to search for novel biological prognostic markers that can stratify high-risk patients likely to experience metastatic disease. Using the above two approaches, we report the development of novel gene signatures that may help to identify patients at a high risk of developing metastatic and progressive disease.

show abstract

Cancer stem/progenitor signatures refine the classification of clear cell renal cell carcinoma with stratified prognosis and decreased immunotherapy efficacy

Cited by 3 publications

References 54 publications

Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma

Cellular specificity of lactate metabolism and a novel lactate-related gene pair index for frontline treatment in clear cell renal cell carcinoma

Cancer Stem Cells in Renal Cell Carcinoma: Origins and Biomarkers

In Vitro and In Silico Analysis of Epithelial-Mesenchymal Transition and Cancer Stemness as Prognostic Markers of Clear Cell Renal Cell Carcinoma

Contact Info

Product

Resources

About