Resection of extensive segments of inferior vena cava without reconstruction in the treatment of renal carcinoma with inferior vena cava tumor thrombus: A case report.

We present a 55-year-old male patient with right renal carcinoma with long inferior vena cava (IVC) tumor thrombus who underwent robot-assisted laparoscopic radical nephrectomy with extensive IVC resection and left renal vein ligation. The patient had a history of hematuria only prior to admission. Our case involved resection of the entire abdominal segment of the IVC and left renal vein without reconstruction. Unfortunately, the patient passed away over a year after the surgery due to brain metastasis.

Enhancing the Efficacy of Radiomics-Based Prediction of Fuhrman Pathological Grading in Renal Clear Cell Carcinoma Using Multilayer Spiral CT Imaging.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma (RCC). Conventional pathological methods of Fuhrman pathological grading system have limitations. This study aims to investigate the efficacy of radiomics-based multilayer spiral computed tomography (CT) imaging of Fuhrman pathological grading in ccRCC. METHODS: A retrospective analysis was conducted on the clinical data of ccRCC patients admitted in our hospital from March 2023 to March 2024. The patients were classified as low-grade (Fuhrman pathological grades I and II) or high-grade (Fuhrman pathological grades III and IV). Statistical methods, including correlation analysis, receiver operating characteristic (ROC) curves and construction of a joint predictive model, were utilised to assess the predictive value of these imaging omics indicators for Fuhrman pathological grading in ccRCC. The primary outcome assessment parameter in this study was the predictive value of these imaging omics indicators for Fuhrman pathological grading in ccRCC. RESULTS: The clinical data from 101 ccRCC patients were examined, with 56 cases classified as low-grade and 45 cases as high-grade. The grey-level co-occurrence matrix (GLCM) features between low and high Fuhrman grading groups, including contrast (0.24 ± 0.08 vs. 0.33 ± 0.09), energy (0.73 ± 0.05 vs. 0.67 ± 0.06) and homogeneity (0.63 ± 0.05 vs. 0.57 ± 0.05), showed notable distinctions (p < 0.001). The CT imaging characteristics between low and high Fuhrman grading groups, including enhancement homogeneity (0.34 ± 0.08 vs. 0.26 ± 0.08) and washout half-time (28.57 ± 4.35 vs. 34.72 ± 5.62) demonstrated a substantial variation between the groups (p < 0.001). The enhancement homogeneity (r = 0.476), washout half-time (r = -0.519), contrast (r = 0.454), energy (r = -0.453) and homogeneity (r = -0.541) showed significant correlations with Fuhrman pathological grading. The predictive value of these features was evident, with a combined imaging genomics model exhibiting an area under the curve of 0.929. CONCLUSIONS: This study demonstrated the potential of radiomics-based prediction using multilayer spiral CT imaging for accurately predicting Fuhrman pathological grading in ccRCC.

Targeted therapies in children with renal cell carcinoma (RCC): An International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG)-related retrospective descriptive study.

INTRODUCTION: Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC. METHODS: This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti-programmed cell death 1 (PD-(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced-stage and relapsed pediatric RCC. RESULTS: Of the 31 identified patients (0-18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT-RCC) (21/31) and the remaining patients mainly presented with papillary or clear-cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono- or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis. CONCLUSION: This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies.

[Clinicopathological features of BAP1 mutated clear cell renal cell carcinoma].

Objective: To investigate the clinicopathological characteristics, immunophenotypes, molecular features, and differential diagnosis of BAP1 mutated clear cell renal cell carcinoma (CCRCC) for better understanding this entity. Methods: Clinical data, histological morphology, immunophenotypes and molecular characteristics of 18 BAP1 mutated CCRCC cases diagnosed at the Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China from January 2020 to December 2022 were analyzed. The patients were followed up. Results: There were 17 males and 1 female patients, aged from 39 to 72 years, with an average age of 56.3 years. Sixteen patients with primary CCRCC were followed up for an average of 24 months, 7 patients had metastases occurred from 4 to 22 months postoperatively. Thirteen of the 16 patients were alive at the time of the last follow-up while 3 patients died 12, 15, and 20 months after the surgery, respectively. One patient underwent retroperitoneal mass resection, but had lung metastasis 32 months after surgery. One case received cervical tumor resection and died at 22 months after the surgery. Characteristic CCRCC regions were identified in 11 of the 18 cases. The tumor cells were arranged in papillary, alveolar, and large nest patterns. Abundant lymphoid tissue, necrosis, and psammoma bodies were seen. Tumor cells showed abundant eosinophilic cytoplasm, and sometimes exhibited rhabdoid differentiation. Round eosinophilic globules were located in the cytoplasm and extracellular matrix. There were 9 cases with WHO/International Society of Urological Pathology grade 3, and 9 cases with grade 4. PAX8 (18/18), carbonic anhydrase 9 (CA9, 16/18), CD10 (18/18), and vimentin (18/18) were positive in the vast majority of tumors.TFE3 was expressed in 5 cases, with strong expression in only 1 case. Eighteen cases were all positive for P504s. Twelve cases harbored a BAP1 mutation combined with von Hippel-Lindau (VHL) mutation, and 2 cases had mutations in BAP1, VHL and PBRM1 simultaneously. SETD2 mutation was not found in any of the cases. Conclusions: BAP1 mutated CCRCC contained papillary, alveolar, and large nest patterns, eosinophilic cytoplasm, high-grade nucleoli, and collagen globules, with P504s positivity. In practical work, when encountering CCRCC containing these features, pathologists should consider the possibility of BAP1 mutations and conduct related molecular tests.

Interaction between microglial cells and CD1C+ B dendritic cells leads to CD8+ T cells depletion during the early stages of renal clear cell carcinoma.

Renal clear cell carcinoma (RCC) is a type of malignant tumor, which, in addition to surgical resection, radiotherapy, and chemotherapy, has been widely treated through immunotherapy recently. However, the influence of the tumor microenvironment and the infiltrating immune cells within it on immunotherapy remains unclear. It is imperative to study the interactions between various immune cells of RCC. The scRNA-seq dataset from GEO's database was used to analyze the immune cells present in tumor tissue and peripheral blood samples. Through quality control, clustering, and identification, the types and proportions of infiltrating immune cells were determined. The cellular differences were determined, and gene expression levels of the differentially present cells were investigated. A protein-protein interaction network analysis was performed using string. KEGG and GO analyses were performed to investigate abnormal activities. The microglia marker CD68 and CD1C+ B dendritic cells marker CD11C were detected using multiplex immunofluorescence staining. Many depleted CD8+ T cells (exhausted CD8+ T cells) appeared in tumor tissues as well as microglia. CD1C+ B dendritic cells did not infiltrate tumor tissues. HSPA1A was correlated with DNAJB1 in microglia. Compared with Paracancer tissues, microglia increased while CD1C+ B dendritic cells decreased in pathological stages I and I-II in cancerous tissues. An altered tumor microenvironment caused by increases in microglia in RCC in the early stage resulted in an inability of CD1C+ B dendritic cells to infiltrate, resulting in CD8+ T cells being unable to receive the antigens presented by them, and in turn being depleted in large quantities.

An integrated bioinformatic investigation of kallikrein gene family members in kidney renel cell carcinoma.

BACKGROUNDS: KLKs have been proved to be key regulators of the tumor microenvironment. In this study, we explored the potential of Kallikrein-related peptidases (KLKs) as clinical diagnostic and prognostic markers in patients with kidney renal clear cell carcinoma (KIRC) as well as their relationship with common immuno-inhibitor and immune cell infiltration in the tumor microenvironment to provide new targets and novel ideas for KIRC therapy. METHODS: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UCSC Xena, Genotype-Tissue Expression (GTEx), Kaplan-Meier plotter, cBioPortal, STRING, GeneMANIA, and TISIDB were used to analyze the differential expression, prognostic value, gene changes, molecular interaction, and immune infiltration of KLKs in patients with KIRC. RESULTS: From the gene expression level, it can be determined that KLK1, KLK6, and KLK7 are differentially expressed in KIRC and normal tissues. From the perspective of clinical prognosis, KLK1, KLK13, and KLK14 are highly correlated with the clinical prognosis of KIRC. The expression of KLKs is regulated by various immunosuppressive agents, with KDR, PVRL2, and VTCN1 being the most significant. The expression of KLKs is significantly correlated with the infiltration of various immune cells, of which Eosinophils and Neutrophils are the most significant. CONCLUSIONS: KLK1, KLK6, KLK7, KLK13, and KLK14 have potential as diagnostic and prognostic biomarkers, among which KLK1 is the most significant. This study may provide detailed immune information and promising targets for KIRC immunotherapy to assist in designing new immunotherapies.

Radiomics nomogram based on CT radiomics features and clinical factors for prediction of Ki-67 expression and prognosis in clear cell renal cell carcinoma: a two-center study.

OBJECTIVES: To develop and validate a radiomics nomogram combining radiomics features and clinical factors for preoperative evaluation of Ki-67 expression status and prognostic prediction in clear cell renal cell carcinoma (ccRCC). METHODS: Two medical centers of 185 ccRCC patients were included, and each of them formed a training group (n = 130) and a validation group (n = 55). The independent predictor of Ki-67 expression status was identified by univariate and multivariate regression, and radiomics features were extracted from the preoperative CT images. The maximum relevance minimum redundancy (mRMR) and the least absolute shrinkage and selection operator algorithm (LASSO) were used to identify the radiomics features that were most relevant for high Ki-67 expression. Subsequently, clinical model, radiomics signature (RS), and radiomics nomogram were established. The performance for prediction of Ki-67 expression status was validated using area under curve (AUC), calibration curve, Delong test, decision curve analysis (DCA). Prognostic prediction was assessed by survival curve and concordance index (C-index). RESULTS: Tumour size was the only independent predictor of Ki-67 expression status. Five radiomics features were finally identified to construct the RS (AUC: training group, 0.821; validation group, 0.799). The radiomics nomogram achieved a higher AUC (training group, 0.841; validation group, 0.814) and clinical net benefit. Besides, the radiomics nomogram provided a highest C-index (training group, 0.841; validation group, 0.820) in predicting prognosis for ccRCC patients. CONCLUSIONS: The radiomics nomogram can accurately predict the Ki-67 expression status and exhibit a great capacity for prognostic prediction in patients with ccRCC and may provide value for tailoring personalized treatment strategies and facilitating comprehensive clinical monitoring for ccRCC patients.

Fc receptor-like A promotes malignant behavior in renal cell carcinoma and correlates with tumor immune infiltration.

BACKGROUND: Our study aims to investigate the mechanisms through which Fc receptor-like A (FCRLA) promotes renal cell carcinoma (RCC) and to examine its significance in relation to tumor immune infiltration. MATERIALS AND METHODS: The correlation between FCRLA and data clinically related to RCC was explored using The Cancer Genome Atlas (TCGA), then validated using Gene Expression Omnibus (GEO) gene chip data. Enrichment and protein-protein interaction (PPI) network analyses were performed for FCRLA and its co-expressed genes. FCRLA was knocked down in RCC cell lines to evaluate its impact on biological behavior. Then the potential downstream regulators of FCRLA were determined by western blotting, and rescue experiments were performed for verification. The relevance between FCRLA and various immune cells was analyzed through GSEA, TIMER, and GEPIA tools. TIDE and ESTIMATE algorithms were used to predict the effect of FCRLA in immunotherapy. RESULTS: Fc receptor-like A was associated with clinical and T stages and could predict the M stage (AUC = 0.692) and 1-3- and 5-year survival rates (AUC = 0.823, 0.834, and 0.862) of RCC patients. Higher expression of FCLRA predicted an unfavorable overall survival (OS) in TCGA-RCC and GSE167573 datasets (p = 0.03, p = 0.04). FCRLA promoted the malignant biological behavior of RCC cells through the pERK1/2/-MMP2 pathway and was associated with tumor immune microenvironment in RCC. CONCLUSION: Fc receptor-like A is positively correlated with poor outcomes in RCC patients and plays an oncogenic role in RCC through the pERK1/2-MMP2 pathway. Patients with RCC might benefit from immunotherapy targeting FCRLA.

Validation and Comparison of Prognostic Models in Renal Carcinoma in a Tertiary Hospital.

BACKGROUND: Renal cell carcinoma (RCC) is the third most frequent urological neoplasia. Proper risk stratification is essential for adequate management. Various calculators are available. This project aims to evaluate the accuracy of the calculators applied to our patients. METHODS: We performed a retrospective study of the nephrectomies due to RCC performed from January 2008 to December 2013. We applied the most widely used predictive models (University of California, Los Angeles Integrated Staging System (UISS), Stage, Size, Grade and Necrosis (SSIGN), Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic RCC Database Consortium (IMDC)) to stratify patients in different risk groups. We evaluated progression-free survival (PFS) or death caused by RCC (cancer-specific survival (CSS)) or other causes (overall survival (OS)). RESULTS: We analysed 238 patients. The 5-year OS, CSS and PFS were 76%, 85% and 83%, whereas the 10-year OS, CSS and PFS were 47%, 75% and 77%, respectively. The 5-year survival analysis by risk groups according to the prognostic models showed that the PFS was 0% and 20.4% in high- and intermediate-risk metastatic RCC (mRCC). Moreover, the PFS was 90%, 95.2% and 98.9% in localised high-, intermediate- and low-risk RCC according to the UISS (area under the receiver operating characteristics curve (AUC): 0.93). The SSIGN model showed a CSS of 99% for the group with the lowest score and 5.3% for the group with the worst prognosis (AUC: 0.91). The OS of mRCC showed medians of 13.25 and 87 months according to MSKCC (AUC: 0.75) and 16, 23 and 85 months according to IMDC (AUC: 0.71) (high risk, intermediate and low). CONCLUSIONS: The validation of the predictive models carried out with our patients showed consistency in many of the results. Risk stratification should be implemented.

ANGPTL4 Suppresses Clear Cell Renal Cell Carcinoma via Inhibition of Lysosomal Acid Lipase.

Renal cell carcinoma (RCC), the most common form of kidney cancer, is a heterogeneous disease with clear cell RCC (ccRCC) being the most prevalent and aggressive subtype. While most ccRCC tumors have elevated expression of angiopoietin-like4 (ANGPTL4), in our study we identified a significant subset of patients whose cancers show no increase in ANGPTL4 expression. These patients have a worse prognosis compared to the patients with high expression of ANGPTL4. These ANGPTL4-low cancers are characterized by the increased frequency of wild-type Von Hippel-Lindau(WT VHL), a gene that is commonly mutated in ccRCC, and an enrichment for genes associated with lipid metabolism. Using RCC tumor models with WT VHL, we demonstrate that ANGPTL4 behaves as a tumor suppressor. The loss of ANGPTL4 in ccRCC cell lines results in increased tumor growth and colony formation in a lysosomal acid lipase (LAL)-dependent manner, a phenotype rescued by the expression of N-terminus ANGPTL4. At the mechanistic level, the loss of ANGPTL4 increases LAL activity in ccRCC cells. These data suggest that ANGPTL4 enacts its tumor-suppressive effects in ccRCC by regulating LAL activity. Importantly, the identified patient cohort with low ANGPTL4 expression may exhibit increased reliance on lipid metabolism, which can be a point of target for future therapy. SIGNIFICANCE: Our data indicate angiopoietin-like 4 (ANGPTL4) acts as a tumor suppressor in clear cell renal cell carcinoma via regulating lipid metabolism and identifies a cohort of patients with lower expression of ANGPTL4 that are correlated with shorter survival.

Predicting tumor mutation burden and VHL mutation from renal cancer pathology slides with self-supervised deep learning.

BACKGROUND: Tumor mutation burden (TMB) and VHL mutation play a crucial role in the management of patients with clear cell renal cell carcinoma (ccRCC), such as guiding adjuvant chemotherapy and improving clinical outcomes. However, the time-consuming and expensive high-throughput sequencing methods severely limit their clinical applicability. Predicting intratumoral heterogeneity poses significant challenges in biology and clinical settings. Our aimed to develop a self-supervised attention-based multiple instance learning (SSL-ABMIL) model to predict TMB and VHL mutation status from hematoxylin and eosin-stained histopathological images. METHODS: We obtained whole slide images (WSIs) and somatic mutation data of 350 ccRCC patients from The Cancer Genome Atlas for developing SSL-ABMIL model. In parallel, 163 ccRCC patients from Clinical Proteomic Tumor Analysis Consortium cohort was used as independent external validation set. We systematically compared three different models (Wang-ABMIL, Ciga-ABMIL, and ImageNet-MIL) for their ability to predict TMB and VHL alterations. RESULTS: We first identified two groups of populations with high- and low-TMB (cut-off point = 0.9). In two independent cohorts, the Wang-ABMIL model achieved the highest performance with decent generalization performance (AUROC = 0.83 ± 0.02 and 0.8 ± 0.04 in predicting TMB and VHL, respectively). Attention heatmaps revealed that the Wang-ABMIL model paid the highest attention to tumor regions in high-TMB patients, while in VHL mutation prediction, non-tumor regions were also assigned high attention, particularly the stromal regions infiltrated by lymphocytes. CONCLUSIONS: Our results indicated that SSL-ABMIL can effectively extract histological features for predicting TMB and VHL mutation, demonstrating promising results in linking tumor morphology and molecular biology.

Frequency of benign tumors after partial nephrectomy and the association between malignant tumor findings and preoperative clinical parameters.

BACKGROUND: Partial nephrectomy (PN) has become the dominant treatment modality for cT1 renal tumor lesions. Tumors suspected of malignant potential are indicated for surgery, but some are histologically classified as benign lesions after surgery. This study aims to analyze the number of benign findings after PN according to definitive histology and to evaluate whether there is an association between malignant tumor findings and individual factors. METHODS: The retrospective study included 555 patients who underwent open or robotic-assisted PN for a tumor in our clinic from January 2013 to December 2020. The cohort was divided into groups according to definitive tumor histology (malignant tumors vs. benign lesions). The association of factors (age, sex, tumor size, R.E.N.A.L.) with the malignant potential of the tumor was further evaluated. RESULTS: In total, 462 tumors were malignant (83%) and 93 benign (17%). Of the malignant tumors, 66% were clear-cell RCC (renal cell carcinoma), 12% papillary RCC, and 6% chromophobe RCC. The most common benign tumor was oncocytoma in 10% of patients, angiomyolipoma in 2%, and papillary adenoma in 1%. In univariate analysis, there was a higher risk of malignant tumor in males (OR 2.13, 95% CI 1.36-3.36, p = 0.001), a higher risk of malignancy in tumors larger than 20 mm (OR 2.32, 95% CI 1.43-3.74, p < 0.001), and a higher risk of malignancy in tumors evaluated by R.E.N.A.L. as tumors of intermediate or high complexity (OR 2.8, 95% CI 1.76-4.47, p < 0.001). In contrast, there was no association between older age and the risk of malignant renal tumor (p = 0.878). CONCLUSIONS: In this group, 17% of tumors had benign histology. Male sex, tumor size greater than 20 mm, and intermediate or high R.E.N.A.L. complexity were statistically significant predictors of malignant tumor findings.

Hexokinase HK3-mediated O-GlcNAcylation of EP300: a key regulator of PD-L1 expression and immune evasion in ccRCC.

Clear cell renal cell carcinoma (ccRCC) demonstrates enhanced glycolysis, critically contributing to tumor development. Programmed death-ligand 1 (PD-L1) aids tumor cells in evading T-cell-mediated immune surveillance. Yet, the specific mechanism by which glycolysis influences PD-L1 expression in ccRCC is not fully understood. Our research identified that the glycolysis-related gene (GRG) HK3 has a unique correlation with PD-L1 expression. HK3 has been identified as a key regulator of O-GlcNAcylation in ccRCC. O-GlcNAcylation exists on the serine 900 (Ser900) site of EP300 and can enhance its stability and oncogenic activity by preventing ubiquitination. Stably expressed EP300 works together with TFAP2A as a co-transcription factor to promote PD-L1 transcription and as an acetyltransferase to stabilize PD-L1 protein. Furthermore, ccRCC exhibits interactive dynamics with tumor-associated macrophages (TAMs). The uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc), which serves as a critical substrate for the O-GlcNAcylation process, facilitates TAMs polarization. In ccRCC cells, HK3 expression is influenced by IL-10 secreted by M2 TAMs. Our study elucidates that HK3-mediated O-GlcNAcylation of EP300 is involved in tumor immune evasion. This finding suggests potential strategies to enhance the efficacy of immune checkpoint blockade therapy.

The role of BUD31 in clear cell renal cell carcinoma: prognostic significance, alternative splicing, and tumor immune environment.

BUD31, a splicing factor, is linked to various cancers. This study examines BUD31's expression, prognostic value, mutation profile, genomic instability, tumor immune environment, and role in clear cell renal cell carcinoma (ccRCC), focusing on cell cycle regulation via alternative splicing. BUD31 expression was analyzed using TCGA and GTEx databases across 33 cancers. Techniques included IHC staining, survival analysis, Cox regression, and nomogram construction. Mutation landscape, genomic instability, and tumor immune microenvironment were evaluated. Functional assays on ccRCC cell lines involved BUD31 knockdown, RNA sequencing, and alternative splicing analysis. BUD31 was upregulated in multiple tumors, including ccRCC. High BUD31 expression correlated with worse survival outcomes and was identified as an independent predictor of poor prognosis in ccRCC. High BUD31 expression also correlated with increased genomic instability and a less active immune microenvironment. BUD31 knockdown inhibited cell proliferation, migration, and invasion in vitro and reduced tumor growth in vivo. RNA sequencing identified 390 alternative splicing events regulated by BUD31, including 17 cell cycle-related genes. KEGG analysis highlighted pathways involved in cell cycle regulation, indicating BUD31's role in promoting cell cycle progression through alternative splicing. BUD31 is upregulated in various tumors and is associated with poor outcomes, increased genomic instability, and a suppressed immune microenvironment in ccRCC. BUD31 promotes cell cycle progression via alternative splicing, suggesting it as a prognostic biomarker and potential therapeutic target in ccRCC.

Impact of tumor multiplicity on the prognosis of patients with primary renal cell carcinoma: a SEER database analysis.

To compare clinical characteristics and survival outcomes of patients with multiple renal cell carcinoma versus single renal cell carcinoma. Develop a prognostic model for predicting prognosis in patients with multiple tumors and analyze prognostic factors. Patients with primary multiple renal cell carcinoma were selected from the Surveillance, Epidemiology, and End Results database (2004-2015). They were divided into single-tumor and multiple-tumor groups. Survival analysis was conducted using the Kaplan-Meier method and log-rank test. A Cox regression model was used to identify potential prognostic factors. A total of 19,489 renal cell carcinoma cases were included, with 947 in the multiple-tumor group and 18,542 in the single-tumor group. The multiple-tumor group had lower cancer-specific survival (P = 0.03, HR = 1.431). Cox regression identified risk factors for the multiple-tumor group including number of tumors, gender, combined summary stage, T stage, N stage, tumor size, and type of surgery. The predicted probabilities showed acceptable agreement with the actual observations at 3-, 5-, and 8-years area under the curve values in both the training and validation cohorts (0.831 vs. 0.605; 0.775 vs. 0.672; and 0.797 vs. 0.699, respectively). Compared with single renal cell carcinoma, multiple renal cell carcinoma is associated with decreased cancer-specific survival. Additionally, we identified several prognostic factors including the number of tumors, T stage, tumor size, and type of surgery. These findings offer valuable insights for selecting appropriate treatment strategies for patients diagnosed with multiple renal cell carcinomas.

Evaluating trophinin associated protein as a biomarker of prognosis and therapy response in renal cell carcinoma.

BACKGROUND: Trophinin Associated Protein (TROAP) has been implicated in some tumors, yet its role in renal cell carcinoma (RCC) remains underexplored. This study aims to elucidate the prognostic and therapeutic implications of TROAP in RCC, encompassing different subtypes. METHODS: Firstly, we identified the expression patterns of TROAP across various tumors within the TCGA pan-cancer cohort. Subsequently, the prognostic significance of TROAP was validated in three TCGA RCC cohorts and a local cohort. Finally, we conducted functional enrichment analysis, somatic mutations and copy number variations, assessed therapeutic response cohorts, and performed in vitro experiments to explore the biological characteristics of TROAP. RESULTS: TROAP serves as an unfavorable factor in both the TCGA RCC datasets and our local cohort. Functional enrichment analysis and in vitro experiments have demonstrated its oncogene effect in promoting tumor progression. Additionally, the relationship between TROAP expression and gene mutations in RCC appears to be limited. Furthermore, elevated TROAP expression is associated with reduced efficacy of RCC therapies, including nivolumab and everolimus. CONCLUSIONS: Our findings illustrate TROAP as a pivotal biomarker for prognosis and therapeutic response in RCC. Elevated TROAP expression is indicative of aggressive tumor behavior and resistance to conventional therapies, making it a valuable target for personalized treatment strategies in RCC management.