Prognostic impact and immunotherapeutic implications of NETosis-related prognostic model in clear cell renal cell carcinoma DOI Creative Commons

Xingjun Mao,

Wen Huang,

Qing Xue

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 27, 2024

Abstract Background The ramifications of necroptosis on the prognostication clear cell renal carcinoma (ccRCC) remain inadequately expounded. Methods A prognostic model delineating facets in ccRCC was constructed, employing a compendium algorithms. External validation effectuated using E-MTAB-1980 dataset. exploration immune infiltration scores undertaken through exploitation multiple Single-cell RNA sequencing data were procured from GSE171306 Real-time quantitative PCR (RT-qPCR) engaged to scrutinize differential expression SLC25A37 across cancer and paracancer tissues, as well diverse lines. Assessments proliferative metastatic alterations 769-P 786-O cells accomplished Cell Counting Kit-8 (CCK8) wound healing assays. Results necroptosis-related signature (NRS) emerges discerning metric, patients’ attributes, tumor mutation burden, immunotherapy response, drug susceptibility. analysis unveils marked enrichment cells. Concurrently, RT-qPCR discloses overexpression both tissues knockdown mitigates propensities cells, evidenced by CCK8 Conclusion NRS assumes pivotal role ascertaining prognosis, susceptibility, features patients. putative player immunosuppressive microenvironments, thereby providing prospective avenue for design innovative immunotherapeutic targets ccRCC.

Language: Английский

The Role of MUC1 in Renal Cell Carcinoma DOI Creative Commons

Martina Milella,

Monica Rutigliano,

Francesco Lasorsa

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 315 - 315

Published: March 7, 2024

Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types cancers. In many human epithelial malignancies, frequently overexpressed, and intracellular activities crucial cell biology. overexpression can enhance cancer proliferation by modulating metabolism. When cells lose their tight connections, due to the loss polarity, mucins become dispersed on both sides membrane, leading an abnormal mucin interactome with membrane. Tumor-related exhibits certain features, such as apical localization aberrant glycosylation that might cause formation tumor-related antigen epitopes. Renal carcinoma (RCC) accounts approximately 3% adult malignancies it most common kidney cancer. The exact this tumor unknown. Evidence suggests may play several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, angiogenesis. purpose review explore meaning tumors particular RCC.

Language: Английский

Citations

37
Ablative Treatments for Small Renal Masses and Management of Recurrences: A Comprehensive Review DOI Creative Commons
Achille Aveta,

Vincenzo Iossa,

Gianluca Spena

et al.

Life, Journal Year: 2024, Volume and Issue: 14(4), P. 450 - 450

Published: March 28, 2024

This review focuses on ablative techniques for small renal masses (SRMs), including radiofrequency ablation (RFA), cryoablation (CA), microwave (MWA), and irreversible electroporation (IRE), discusses recurrence management. Through an extensive literature review, we outline the procedures, outcomes, follow-up strategies associated with each method. The provides a detailed examination of these techniques-RFA, CA, MWA, IRE-elucidating their respective outcomes. Recurrence rates vary among them, RFA CA showing comparable rates, MWA demonstrating favorable short-term results, IRE exhibiting promise in experimental stages. For managing recurrences, various are considered, active surveillance, re-ablation, or salvage surgery. Surveillance is preferred post-RFA post-CA, due to slow SRM growth, while particularly deemed feasible without additional complications. Salvage surgery emerges as viable option larger resistant tumors. While offer results surgery, further research essential understand long-term effects fully. Decisions concerning management should consider individual tumor-specific factors. Imaging, notably contrast-enhanced ultrasounds, plays pivotal role assessing treatment success, emphasizing necessity multidisciplinary approach optimal lack randomized trials highlights need research.

Language: Английский

Citations

19
Complement C3 of tumor-derived extracellular vesicles promotes metastasis of RCC via recruitment of immunosuppressive myeloid cells DOI Creative Commons

Yibi Zhang,

Xiaodong Wang,

Yinmin Gu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(4)

Published: Jan. 23, 2025

Heterogeneous roles of complement C3 have been implicated in tumor metastasis and are highly context dependent. However, the underlying mechanisms linking to remain elusive renal cell carcinoma (RCC). Here, we demonstrate that RCC cell-derived extracellular vesicles (EVs) contributes via polarizing tumor-associated macrophages (TAMs) into immunosuppressive phenotype recruiting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, EV induces secretion CCL2 CXCL1 by lung subsequently enhances TAM polarization PMN-MDSC recruitment. Notably, targeting CCL2/CCR2 or CXCL1/CXCR2 axis with inhibitors RS504393 Navarixin, respectively, effectively suppresses induced RCC-derived a mouse model. Clinically, patients high expression poor prognosis. Collectively, our findings reveal tumor-derived an microenvironment TAMs, thus promoting metastasis.

Language: Английский

Citations

4
Ischemia–Reperfusion Injury in Kidney Transplantation: Mechanisms and Potential Therapeutic Targets DOI Open Access
Francesco Lasorsa,

Monica Rutigliano,

Martina Milella

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4332 - 4332

Published: April 14, 2024

Kidney transplantation offers a longer life expectancy and better quality of than dialysis to patients with end-stage kidney disease. Ischemia–reperfusion injury (IRI) is thought be cornerstone in delayed or reduced graft function increases the risk rejection by triggering immunogenicity organ. IRI an unavoidable event that happens when blood supply temporarily then restored result several biological pathways, such as transcriptional reprogramming, apoptosis necrosis, innate adaptive immune responses, endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) β-oxidation for energy production since more ATP molecules are yielded per substrate molecule glucose oxidation. Upon ischemia–reperfusion damage, system activates achieve tissue clearance repair. Several cells, cytokines, enzymes, receptors, ligands known take part these events. The complement cascade might start even before organ procurement deceased donors. However, additional experimental clinical data required understand pathogenic events place during this complex process.

Language: Английский

Citations

15
Transcriptomic and proteo-metabolic determinants of the grading system in clear cell renal cell carcinoma DOI Creative Commons
Giuseppe Lucarelli, Francesco M. Lasorsa,

Martina Milella

et al.

Urologic Oncology Seminars and Original Investigations, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

2
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

2
Novel insights into molecular landscape of advanced renal cell carcinoma DOI
Giuseppe Lucarelli, Francesco M. Lasorsa

ONCOLOGIE, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

Citations

1
Targeting the complement system: notes on therapeutic strategies for renal cancer DOI
Francesco Lasorsa,

Monica Rutigliano,

Martina Milella

et al.

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 3

Published: April 25, 2025

Language: Английский

Citations

1
Crosstalk of disulfidptosis-related subtypes identifying a prognostic signature to improve prognosis and immunotherapy responses of clear cell renal cell carcinoma patients DOI Creative Commons
Lei Ren, Jinwen Liu,

Qingyuan Lin

et al.

BMC Genomics, Journal Year: 2024, Volume and Issue: 25(1)

Published: April 26, 2024

Abstract Background Disulfidptosis is a novel form of programmed cell death induced by high SLC7A11 expression under glucose starvation conditions, unlike other known forms death. However, the roles disulfidptosis in cancers have yet to be comprehensively well-studied, particularly ccRCC. Methods The profiles and somatic mutation DGs from TCGA database were investigated. Two clusters identified unsupervised consensus clustering analysis, disulfidptosis-related prognostic signature (DR score) was constructed. Furthermore, predictive capacity DR score prognosis validated several clinical cohorts. We also developed nomogram based on features. Then, we investigated differences clinicopathological information, TMB, tumor immune landscapes, biological characteristics between high- low-risk groups. evaluated whether robust tool for predicting immunotherapy response TIDE algorithm, checkpoint genes, submap CheckMate cohort. Results two with significant prognosis, has been demonstrated as an independent risk factor high-risk group patients had more complicated microenvironment suffered evasion immunotherapy. Moreover, better immunotherapy, anti-PD1 anti-CTLA-4 inhibitors, which verified Conclusion can accurately predict assist clinicians providing personalized treatment regime ccRCC patients.

Language: Английский

Citations

4
Screening of differential gene expression patterns through survival analysis for diagnosis, prognosis and therapies of clear cell renal cell carcinoma DOI Creative Commons

Alvira Ajadee,

Sabkat Mahmud,

Md Bayazid Hossain

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(9), P. e0310843 - e0310843

Published: Sept. 30, 2024

Clear cell renal carcinoma (ccRCC) is the most prevalent subtype of kidney cancer. Although there increasing evidence linking ccRCC to genetic alterations, exact molecular mechanism behind this relationship not yet completely known researchers. Though drug therapies are best choice after metastasis, unfortunately, majority patients progressively develop resistance against therapeutic drugs receiving it for almost 2 years. In case, multi-targeted different variants essential effective treatment ccRCC. To understand mechanisms development and progression, explore drugs, identify ccRCC-causing key genes (KGs). order obtain KGs, at first, we detected 133 common differentially expressed (cDEGs) between control samples based on nine (9) microarray gene-expression datasets with NCBI accession IDs GSE16441, GSE53757, GSE66270, GSE66272, GSE16449, GSE76351, GSE66271, GSE71963, GSE36895. Then, filtered these cDEGs through survival analysis independent TCGA GTEx database obtained 54 scDEGs having significant prognostic power. Next, used protein-protein interaction (PPI) network reduced set top-ranked eight KGs ( PLG , ENO2 ALDOB UMOD ALDH6A1 SLC12A3 SLC12A1 SERPINA5 ). The pan-cancer showed association subtypes cancers including gene regulatory (GRN) revealed some crucial transcriptional post-transcriptional regulators KGs. scDEGs-set enrichment significantly identified functions, biological processes, cellular components, pathways that linked results DNA methylation study indicated hypomethylation hyper-methylation which may lead immune infiltrating types (CD8+ T CD4+ cell, B neutrophil, dendritic macrophage) their in ccRCC, where positively correlated cells, but negatively other supported by literature review also. Then 10 repurposable molecules (Irinotecan, Imatinib, Telaglenastat, Olaparib, RG-4733, Sorafenib, Sitravatinib, Cabozantinib, Abemaciclib, Dovitinib.) docking KGs-mediated receptor proteins. Their ADME/T cross-validation receptors, also potent Therefore, outputs might be useful inputs/resources wet-lab researchers clinicians considering an strategy

Language: Английский

Citations

4