PRCC (Proline Rich Mitotic Checkpoint Control Factor)

PABPC1 could serve as a potential prognostic biomarker for individuals with KIRP.

Importantly, dual inhibition of the autophagy and mTOR pathways synergistically suppressed tumor growth, exceeding the efficacy of single-agent treatments. These data demonstrate that co-targeting these TFE3-regulated pathways represents a promising therapeutic strategy for this intractable malignancy.

Taken together, tRCC fusion proteins upregulate B7-H3 expression via increased mTOR signaling, resulting in a higher tumoral B7-H3 expression compared to normal kidney or conventional RCC, suggesting that B7-H3 may be a promising therapeutic target in tRCC.

Furthermore, it was shown that the increased NAD+ metabolism driven by NMRK2 enhanced the stability of CD38 protein through SIRT1-mediated deacetylation, which underlines impairment of CD8+T cells and the development of an immunosuppressive state in PRCC-TFE3 rRCC. Our findings not only elucidated a mechanism underlying immunological ignorance in PRCC-TFE3 rRCC but also propose potential therapeutic targets.

To evaluate the expression of trophoblast cell surface antigen-2 (TROP-2), a broadly expressed antibody-drug conjugate (ADC) target, in non-clear cell renal cell carcinoma (nccRCC), and to perform a proof-of-concept analysis assessing the cytotoxic efficacy of the TROP-2-directed ADC Sacituzumab govitecan (SG) in RCC cell lines...These findings support further investigation of TROP-2-directed ADCs, such as SG, in patients with metastatic TROP-2-positive pRCC. The online version contains supplementary material available at 10.1007/s00345-025-05880-2.

This disruption of lipid homeostasis in clear cell renal carcinoma (pRCC), particularly in mitochondrial cardiolipin metabolism, inhibited mitochondria-dependent apoptosis and, consequently, enhanced tumorigenesis. These findings suggest TRIM59 as a biomarker and potential therapeutic target, supporting precision oncology strategies for pRCC treatment.

However, close follow-up is necessary owing to a high risk of recurrence and metastasis. Targeted therapies and immunotherapies are potential treatment options for patients with advanced or metastatic disease.

This study underscores the critical role of TPX2 in type 2 pRCC progression and highlights its potential as a prognostic biomarker and therapeutic target. The TPX2/LINC00894/miR-660-5p regulatory axis provides novel insights into the molecular mechanisms driving pRCC and offers a promising avenue for improving patient prognosis.

We further show that tRCC tumor aggressiveness is related to their EMT and their associated enrichment in myofibroblast cancer-associated fibroblasts (myCAFs) that are both hallmarks of poor prognostic outcomes. We define tRCC as a novel metabolic subtype of renal cancer and provide unique insights into how broad genomic binding of TFE3 fusion proteins regulates OxPhos and ferroptosis resistance.

A combined receiver operating characteristic (ROC) curve analysis revealed that the BCL11A-NTN5-OGN genes, which have specificity and sensitivity values of 0.968 and 0.901, respectively, can be used as a diagnostic biomarker for PRCC. In general, the genes introduced in this study may be used as diagnostic biomarkers for the early diagnosis of PRCC, thus providing the possibility of early treatment and preventing the progression of the disease.

The fusion partner gene ZC3H4 is uncommon, and this is the third reported PEComa case. The fusion partner gene PRCC is often reported in TFE3-rearranged renal cell carcinoma, and this PEComa case is the second reported in the head and neck region. The initially reported cases with the fusion partner genes ZC3H4 and PRCC were categorized as malignant. These cases were discussed with a literature review.

RNA-seq and metabolomic analyses of the kidney tissues from these mice revealed that ketone body production is inversely correlated with tumor development, whereas de novo lipid synthesis is upregulated through the HIF1α/SREBP1-dependent mechanism in TFE3-RCC. Our data suggest that the coordinated metabolic shift via the PRCC-TFE3/HIF1α/SREBP1 axis is a key mechanism by which PRCC-TFE3 enhances cancer cell metabolism, promoting tumor development in TFE3-RCC.