Exploring the Prognostic Value of Tumour‐Associated Genes in Clear Cell Renal Cell Carcinoma Through Single‐Cell RNA Sequencing Insights DOI Creative Commons

Tongfei Fu,

Xinyi Zhang,

Yuedong Liu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(24)

Published: Dec. 1, 2024

ABSTRACT Clear cell renal carcinoma (ccRCC) characterised by its diversity and a tendency to defy standard therapeutic approaches. Amidst the advent of immunotherapy, it has become imperative pinpoint prognostic indicators tumour microenvironment (TME) influence efficacy treatments. Employing single‐cell RNA sequencing (scRNA‐seq), this research delved into diverse landscape ccRCC, uncovering complex underpinnings pinpointing molecular avenues for intervention. We constructed model using 101 machine learning algorithms integrated data from multiple cohorts, including TCGA, ICGC, microarray datasets. The model's was assessed Concordance Index (C‐index), further analyses included pseudotime analysis cells, mutation correlation between immunity. model, combining Lasso regression survival Support Vector Machine (SVM), demonstrated robust discrimination with C‐index 0.650. Investigation TME uncovered pronounced associations presence immune infiltrates patient outcomes, notable emphasis on impact CCL2‐expressing neoplastic cells. GO Biological Processes (GOBP) encompass regulation endothelial maturation, formation layers, enhancement gene expression controlled Notch receptors, development barriers. effectively pinpointed critical markers crafted forecasting that achieved 0.650, highlighting significant infiltration, especially CCL2+ ccRCC prognosis.

Language: Английский

First Single-Centre Experience with the Novel HIF-α Inhibitor Belzutifan in Switzerland DOI Creative Commons
Tobias Peres, Stefanie Aeppli, Stefanie Fischer

et al.

Current Oncology, Journal Year: 2025, Volume and Issue: 32(2), P. 64 - 64

Published: Jan. 26, 2025

Belzutifan is a new HIF-α inhibitor mainly used in two different indications: von Hippel–Lindau syndrome-associated renal cell carcinoma, haemangioblastomas and pancreatic neuroendocrine tumours, as well sporadic advanced pre-treated carcinoma. Although efficacy has been demonstrated phase II III studies, belzutifan still not approved many countries. In addition, syndrome rare disease. Therefore, there virtually no real-world experience data of available. We aim to determine the tolerability patients with tumours tyrosine kinase- immune checkpoint inhibitors for A retrospective analysis five treated between 2023 2024 at Swiss cancer centre was conducted. this case series, all consistently benefitted from response treatment. This series provides evidence that an effective well-tolerated treatment option

Language: Английский

Citations

1
The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma DOI Creative Commons
Yifan Zhang, Shengli Zhang, Hongbin Sun

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 19, 2025

Abstract Renal cell carcinoma (RCC), a therapeutically recalcitrant genitourinary malignancy, exemplifies the profound interplay between oncogenic signaling and metabolic adaptation. Emerging evidence positions reprogramming as central axis of RCC pathogenesis, characterized by dynamic shifts in nutrient utilization that transcend canonical Warburg physiology to encompass lipid anabolism, glutamine auxotrophy, microenvironment-driven plasticity. This orchestrated rewiring cellular energetics sustains tumor proliferation under hypoxia while fostering immunosuppression through metabolite-mediated T exhaustion myeloid-derived suppressor activation. Crucially, exhibits heterogeneity across histological subtypes intratumoral regions—a feature increasingly recognized determinant therapeutic resistance. Our review systematically deciphers molecular architecture metabolism, elucidating how VHL/HIF mutations, mTOR pathway dysregulation, epigenetic modifiers converge reshape glucose flux, droplet biogenesis, amino acid catabolism. We present novel insights into spatial zonation within tumors, where pseudohypoxic niches engage lactate shuttling cholesterol efflux adjacent vasculature, creating pro-angiogenic immunosuppressive microdomains. Therapeutically, we evaluate first-in-class inhibitors targeting rate-limiting enzymes de novo lipogenesis proposing biomarker-driven strategies overcome compensatory highlight synergy glutaminase PD-1 blockade reinvigorating CD8 + function, role lipid-loaded cancer-associated fibroblasts shielding tumors from ferroptosis. Finally, outline translational roadmap integrating multi-omics profiling, functional metabolomics, biology match vulnerabilities with precision therapies.

Language: Английский

Citations

1
O-GlcNAcylation regulation of RIPK1-dependent apoptosis dictates sensitivity to sunitinib in renal cell carcinoma DOI
Xiangbo Zeng, Zhiliang Chen, Yuanchao Zhu

et al.

Drug Resistance Updates, Journal Year: 2024, Volume and Issue: 77, P. 101150 - 101150

Published: Sept. 12, 2024

Language: Английский

Citations

5
Molecular imaging of renal cell carcinomas: ready for prime time DOI

Qianyun Wu,

Hongda Shao, Wei Zhai

et al.

Nature Reviews Urology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 14, 2024

Language: Английский

Citations

4
Identification of a novel prognostic and therapeutic prediction model in clear cell renal carcinoma based on Renin-angiotensin system related genes DOI Creative Commons

Qinzheng Chang,

Shuo Zhao, Jiajia Sun

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Background Clear cell renal carcinoma is the most predominant type of malignancies, characterized by high aggressiveness and probability distant metastasis. Renin angiotensin system (RAS) plays a crucial role in maintaining fluid balance within human body, its involvement tumorigenesis increasingly being uncovered, while ccRCC remains unclear. Methods WGCNA was used to identify RAS related genes. Machine learning applied screen hub genes for constructing risk model, E-MTAB-1980 dataset external validation. Transwell CCK8 assays were investigate impact SLC6A19 cells. Results SLC6A19, SLC16A12 SMIM24 eventually screened construct model predictive efficiency prognosis validated internal cohorts. Moreover, differences found pathway enrichment, immune infiltration, mutational landscapes drug prediction between low groups. Experimental results indicated that could inhibit invasion proliferation cells GSEA pinpointed intimately correlated with fatty acid metabolism CPT1A. Conclusion The based on three RAS-related have robust ability predict sensitivity patients, further providing valid instruction clinical care.

Language: Английский

Citations

0
Hypoxia-induced NDRG1 C-terminal Poly-phosphorylation Impairs its Tumor Suppressor Function in Renal Cell Carcinoma DOI

Qiang Guo,

Meiyu Quan,

Jingyu Zheng

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: 619, P. 217659 - 217659

Published: March 24, 2025

Language: Английский

Citations

0
Decoding the genetic puzzle: Mutations in key driver genes of pancreatic neuroendocrine tumors DOI

Huanchang Jiang,

Wuhu Zhang,

Xiaowu Xu

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189305 - 189305

Published: March 1, 2025

Language: Английский

Citations

0
Increased ZNF83 is a potential prognostic biomarker and regulates oxidative stress-induced ferroptosis in clear cell renal cell carcinoma DOI
Zhaojie Lyu,

Huming Wang,

Fang Dai

et al.

Journal of Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

Language: Английский

Citations

0
CD70-targeted cancer theranostics: Progress and challenges DOI
Weijun Wei, Viktor Grünwald,

Ken Herrmann

et al.

Med, Journal Year: 2025, Volume and Issue: unknown, P. 100671 - 100671

Published: April 1, 2025

Language: Английский

Citations

0
Identification of Molecular Subtypes of Clear-Cell Renal Cell Carcinoma in Patient-Derived Xenografts Using Multi-Omics DOI Open Access

Zhengyuan Qiu,

Dalin Zhang,

Fernando Jose Garcia-Marques

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(8), P. 1361 - 1361

Published: April 18, 2025

Background/Objectives: Clear-cell renal cell carcinoma (ccRCC) is a heterogenous disease that can be classified into multiple molecular subtypes with differential prognosis and sensitivities to treatments based on their genomic, transcriptomic, proteomic, metabolic profiles. Patient-derived xenografts (PDXs) are high-fidelity cancer models because they maintain similar genotypes immunohistologic phenotypes the parental tumors respond standard-of-care therapies as expected. However, whether identified in ccRCC patient samples preserved PDX not clear. Our objective compare transcriptional proteomic profiles of our those patients identify both similarities distinctions between corresponding subtypes, so proper used when investigating subtypes. Methods: To match PDXs human we compared transcriptomic five established lab reported by group, well other groups, using hierarchical analysis, Principal Component Analysis (PCA), Permutation Correlation Analysis. The enrichment key pathways was determined Gene Set Enrichment Results: We found each resembles one closely at transcript protein levels. In addition, representing different show unique characteristics. Moreover, correlated pathway activities implicated progression therapy resistance. Conclusions: results suggest should mechanism resistance for This “matching” strategy will greatly facilitate clinical translation positive findings optimal management patients.

Language: Английский

Citations

0