Clear Cell Renal Cell Carcinoma

These differences may reflect the limitations of body mass index as a biological indicator of obesity, together with variations in systemic inflammation, body composition, and treatment context. Here, we summarize current knowledge on obesity-driven immunometabolic rewiring in RCC and outline key priorities for the field, including obesity-relevant preclinical models, biomarkers of visceral adiposity and systemic inflammation, and clinical trials targeting immunometabolism.

This feasibility study demonstrates that ccRCC organoid generation from surgical specimens is achievable but remains limited by variable establishment rates and culture duration. Further optimization and integration of microenvironmental components will be necessary to enhance the translational relevance of this model.

Elevated miR34a levels may contribute to podocyte injury by inhibiting KLF4, thereby promoting the progression of obesity-related glomerulopathy. miR34a may also be related to the pathogenesis of ccRCC, especially in obese patients.

GSCA/GDSC-based drug sensitivity prediction suggested that high KIF7 expression was associated with increased predicted sensitivity to docetaxel and bleomycin, whereas no significant association was observed for I-BET-762. Additionally, it was associated with shaping the immune microenvironment. These findings highlight KIF7 as a potential prognostic biomarker and therapeutic target in ccRCC.

Awareness of such presentations is crucial, particularly in patients with a known history of ccRCC, as these lesions may clinically and radiologically mimic primary tumours of the affected sites. Careful evaluation of its histomorphological features and judicious use of immunohistochemical panels, together with clinical and radiological correlations, is the key to arriving at an accurate diagnosis.

AQP1 overexpression suppressed proliferation, migration, invasion, and xenograft growth, accompanied by upregulation of TNF-α, TNFRSF1A, Bax, and Cleaved Caspase-3 and reduced Vimentin, suggesting activation of TNF-related pro-apoptotic signaling. AQP1 is epigenetically silenced in ccRCC and suppresses tumor growth via TNF-mediated apoptosis, establishing it as an independent prognostic biomarker and candidate therapeutic target.

These findings represent computational predictions derived from transcriptomic and survival associations rather than direct evidence of therapeutic efficacy. The study provides a reproducible pan-cancer strategy for prioritizing candidate cancer types for future mechanistic and experimental validation of traditional Chinese medicine formulations.

Using the Seahorse XFe96 analyzer we also showed reduced glycolytic capacity and reserve in RCC4-ATF4 KO cells. Collectively, our results demonstrate that ATF4 regulates glycolysis in ccRCC, supporting ATF4 as a therapeutic target.

Importantly, combination treatment with olaparib and sunitinib showed superior antitumor efficacy in ccRCC PDOs. This study demonstrates that PARP9 promotes sunitinib resistance in ccRCC by activating the STAT1/IRF1 pathway and upregulating ISG15/IFIT1.

By integrating evidence from cytokine profiling in tumor tissue, plasma, and urine with current knowledge of STAT3 signaling, this review highlights the importance of compartment-specific inflammatory signatures in understanding ccRCC biology and their potential relevance for biomarker discovery. Integrative approaches combining cytokine profiling with functional assessment of STAT3 activation may improve disease characterization and support the development of diagnostic and prognostic biomarkers, although rigorous clinical validation remains necessary.

Single-cell transcriptomic analyses further resolved cell-type-specific expression patterns, distinguishing tumor-intrinsic from immune-restricted expression profiles. Collectively, our findings establish CD70, CD80, and TIGIT as integrative biomarkers of tumor progression, immune contexture, and therapeutic response, providing a rationale for their clinical exploitation in precision immuno-oncology.

Loss of BAP1 or PBRM1 identifies a biologically aggressive ccRCC subset with worse oncological outcomes. IHC-based molecular profiling is a practical and accessible tool for risk stratification in surgically treated ccRCC.