Cancer marker TNFRSF1A: From single­cell heterogeneity of renal cell carcinoma to functional validation.

During the progression of renal cell carcinoma (RCC), tumor growth, metastasis and treatment response heterogeneity are regulated by both the tumor itself and the tumor microenvironment (TME). The aim of the present study was to investigate the role of the TME in RCC and construct a crosstalk network for clear cell RCC (ccRCC). An additional aim was to evaluate whether TNF receptor superfamily member 1A (TNFRSF1A) is a potential therapeutic target for ccRCC. Single-cell data analysis of RCC was performed using the GSE152938 dataset, focusing on key cellular components and their involvement in the ccRCC TME. Additionally, cell-cell communication was analyzed to elucidate the complex network of the ccRCC microenvironment. Analyses of data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium databases were performed to further mine the key TNF receptor genes, with a particular focus on the prediction and assessment of the cancer-associated features of TNFRSF1A. In addition, following the silencing of TNFRSF1A using small interfering RNA in the 786-O ccRCC cell line, a number of in vitro experiments were conducted to further investigate the cancer-promoting characteristics of TNFRSF1A. These included 5-ethynyl-2'-deoxyuridine incorporation, Cell Counting Kit-8, colony formation, Transwell, cell cycle and apoptosis assays. The TNF signaling pathway was found to have a critical role in the development of ccRCC. Based on the specific crosstalk identified between TNF and TNFRSF1A, the communication of this signaling pathway within the TME was elucidated. The results of the cellular phenotype experiments indicated that TNFRSF1A promotes the proliferation, migration and invasion of ccRCC cells. Consequently, it is proposed that targeting TNFRSF1A may disrupt tumor progression and serve as a therapeutic strategy. In conclusion, by understanding the TME and identifying significant crosstalk within the TNF signaling pathway, the potential of TNFRSF1A as a therapeutic target is highlighted. This may facilitate an advance in precision medicine and improve the prognosis for patients with RCC.

Choroidal Metastasis From Papillary Renal Cell Carcinomas: A Case Report and a Review of the Literature.

Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in the English literature as of January 31, 2024. Nevertheless, physicians need to be vigilant in recognizing this condition, as its progression impacts the quality of life (QOL) of affected patients. In Case 1, a 60-year-old male with a medical history of papillary RCC experienced a deterioration in visual acuity (VA) and was diagnosed with solitary choroidal metastasis. Subsequently, multiple metastases were identified, prompting the initiation of a combination therapy regimen consisting of pembrolizumab plus axitinib. Despite treatment, progression of choroidal metastasis and a further decline in VA were observed. The patient underwent stereotactic radiotherapy and experienced complete resolution of the choroidal metastasis, accompanied by a slight improvement in VA. In Case 2, a 76-year-old man presented with a renal tumor accompanied by lung metastases. He underwent nephrectomy, and the histological diagnosis was papillary RCC. We initiated combination therapy consisting of nivolumab plus cabozantinib. The patient experienced a decrease in VA during treatment. We identified extensive fine metastases scattered throughout the bilateral choroid. We administered axitinib, but the patient experienced bilateral blindness. Given the absence of established therapy for choroidal metastasis, it is crucial to maintain flexibility in treatment selection. Local or systemic approaches should be used as deemed appropriate for each individual case.

Establishment and validation of a novel disulfidptosis-related immune checkpoint gene signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal tumors and is associated with a unfavorable prognosis. Disulfidptosis is a recently identified form of cell death mediated by disulfide bonds. Numerous studies have highlighted the significance of immune checkpoint genes (ICGs) in ccRCC. Nevertheless, the involvement of disulfidptosis-related immune checkpoint genes (DRICGs) in ccRCC remains poorly understood. METHODS: The mRNA expression profiles and clinicopathological data of ccRCC patients were obtained from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. The associations between disulfidptosis-related genes (DRGs) and immune checkpoint genes (ICGs) were assessed to identify DRICGs. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were conducted to construct a risk signature. RESULTS: A total of 39 differentially expressed immune-related candidate genes were identified. A prognostic signature was constructed utilizing nine DRICGs (CD276, CD80, CD86, HLA-E, LAG3, PDCD1LG2, PVR, TIGIT, and TNFRSF4) and validated using GEO data. The risk model functioned as an independent prognostic indicator for ccRCC, while the associated nomogram provided a reliable scoring system for ccRCC. Gene set enrichment analysis indicated enrichment of phospholipase D, antigen processing and presentation, and ascorbate and aldarate metabolism-related signaling pathways in the high-risk group. Furthermore, the DRICGs exhibited correlations with the infiltration of various immune cells. It is noteworthy that patients with ccRCC categorized into distinct risk groups based on this model displayed varying sensitivities to potential therapeutic agents. CONCLUSIONS: The novel DRICG-based risk signature is a reliable indicator for the prognosis of ccRCC patients. Moreover, it also aids in drug selection and correlates with the tumour immune microenvironment in ccRCC.

Molecular subtypes of clear cell renal carcinoma based on PCD-related long non-coding RNAs expression: insights into the underlying mechanisms and therapeutic strategies.

BACKGROUND: PCD-related long non-coding RNAs (PRLs) are rarely investigated in relation to clear cell renal carcinoma (ccRCC). As part of this study, we evaluated the immunological potential of PRL signatures as a biomarker for ccRCC prognosis and immunological function. MATERIALS AND METHODS: Data were downloaded from the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases. A Pearson correlation analysis was conducted on the 27 PCD-associated genes to determine whether lncRNAs were significantly associated with PCD. Kaplan-Meier analysis, biological function identification, immune infiltration analysis, estimation of efficacy of immunotherapy and targeted drug screening, and exploration of the landscape of mutation status were conducted by analyzing the risk scores. RESULTS: Seven PRLs, LINC02747, AP001636.3, AC022126.1, LINC02657, LINC02609, LINC02154, and ZNNT1, were used to divide patients with ccRCC into groups with high and low risk. High-risk patients had a worse prognosis than low-risk patients, according to the results, and the PRL signature showed promising predictive ability. More immune cells were clustered in the high-risk group, whereas the immune cell function of the low-risk group was significantly suppressed. The high-risk group was less sensitive to immunotherapy, whereas the low-risk group had positive responses to most drugs. CONCLUSIONS: Collectively, we established and verified a PRL signature that could competently guide the prognostic survival and immunotherapy of ccRCC. In addition, molecular subtypes were determined for ccRCC based on PRL expression, which may help elucidate the underlying molecular mechanism of ccRCC and develop targeted treatments.

ZNF692 promotes the migration and response to immunotherapy of clear cell renal cell carcinoma cells by targeting metabolic pathway.

Clear cell renal cell carcinoma (ccRCC), with high mortality and poor prognosis, is the most common type of renal malignancy. It is necessary to identify new biomarkers that can serve as indicators for the detection of ccRCC at its early stages. In this study, we analyzed the role of classical zinc finger protein 692 (ZNF692) in ccRCC using datasets from The Cancer Genome Atlas (TCGA) and Single Cell Portal and immunohistochemical (IHC) staining of a tissue-microarray, and analyzed the function of ZNF692 in ccRCC cells. The analyses indicated that ZNF692 was upregulated in ccRCC samples compared with normal or paracancerous control samples (P < 0.001) and that the expression of this gene was linked to poor overall survival (HR = 2.1, P < 0.0001). The knockdown of ZNF692 inhibited the proliferation and migration of ccRCC cells by target GTPase-activating protein (SH3 domain)-binding protein 2 (G3BP2), and transmembrane 9 superfamily member 2 (TM9SF2)). T, B, proximal, and collecting tubule cells are the dominant cell types in normal kidney tissue where ZNF692 is expressed. In addition, immune checkpoint blockade (ICB) therapy dramatically changed the expression patterns of ZNF692. Collectively, these data indicate that ZNF692 may serve as prognosis, and as a potential indicator of the response to ICB therapy, a possibility needs to be verified by a case‒control study.

Synchronous occurrence of primary breast cancer and renal cell carcinoma: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Multiple Primary Malignant Neoplasms (MPMNs) are rare and refer to the occurrence of two or more distinct primary cancers with unrelated histopathological features in one patient. MPMNs can be classified as synchronous when tumors appear simultaneously or within six months of each other, and as metachronous when identified six months or more after the initial cancer diagnosis. While breast cancer often co-occurs with other primary cancers such as colorectal, endometrial, and ovarian cancers, the simultaneous presence of invasive lobular breast carcinoma and clear cell renal cancer is rare. CASE PRESENTATION: Here, we present the case of a 59-year-old postmenopausal woman who initially presented with breast carcinoma. Further investigation revealed a mass in the left kidney. The patient underwent a radical mastectomy and axillary dissection, followed by a left nephrectomy. After 8 months follow up, the patient is doing well and disease-free. CLINICAL DISCUSSION: Based on our case and literature review, the co-occurrence of breast carcinoma with renal cell carcinoma (RCC) is uncommon. Most reported cases involve metastatic tumors or metachronous breast malignancy with RCC. The etiology of synchronous malignancy is complex, and treatment options usually include a combination of surgery and/or adjuvant therapy. CONCLUSION: This case report contributes valuable insights to the limited literature on synchronous breast cancer with renal cell carcinoma. The rarity of this simultaneous occurrence underscores the importance of considering such cases. Documenting these cases is crucial for increasing awareness and reducing the resulting morbidity and mortality.

Characterization of a G2M checkpoint-related gene model and subtypes associated with immunotherapy response for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) presents challenges in early diagnosis and effective treatment. In this study, we aimed to establish a prognostic model based on G2M checkpoint-related genes and identify associated clusters in ccRCC through clinical bioinformatic analysis and experimental validation. Utilizing a single-cell RNA dataset (GSE159115) and bulk-sequencing data from The Cancer Genome Atlas (TCGA) database, we analyzed the G2M checkpoint pathway in ccRCC. Differential expression analysis identified 45 genes associated with the G2M checkpoint, leading to the construction of a predictive model with four key genes (E2F2, GTSE1, RAD54L, and UBE2C). The model demonstrated reliable predictive ability for 1-, 3-, and 5-year overall survival, with AUC values of 0.794, 0.790, and 0.794, respectively. Patients in the high-risk group exhibited a worse prognosis, accompanied by significant differences in immune cell infiltration, immune function, TIDE and IPS scores, and drug sensitivities. Two clusters of ccRCC were identified using the "ConsensusClusterPlus" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. Targeted experiments on RAD54L, a gene involved in DNA repair processes, revealed its crucial role in inhibiting proliferation, invasion, and migration in 786-O cells. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.

CT-based radiomics model using stability selection for predicting the World Health Organization/International Society of Urological Pathology grade of clear cell renal cell carcinoma.

OBJECTIVES: This study aimed to develop a model to predict World Health Organization/International Society of Urological Pathology (WHO/ISUP) low-grade or high-grade clear cell renal cell carcinoma (ccRCC) using 3D multiphase enhanced CT radiomics features (RFs). METHODS: CT data of 138 low-grade and 60 high-grade ccRCC cases were included. RFs were extracted from four CT phases: non-contrast phase (NCP), corticomedullary phase, nephrographic phase, and excretory phase (EP). Models were developed using various combinations of RFs and subjected to cross-validation. RESULTS: There were 107 RFs extracted from each phase of the CT images. The NCP-EP model had the best overall predictive value (AUC = 0.78), but did not significantly differ from that of the NCP model (AUC = 0.76). By considering the predictive ability of the model, the level of radiation exposure, and model simplicity, the overall best model was the Conventional image and clinical features (CICFs)-NCP model (AUC = 0.77; sensitivity 0.75, specificity 0.69, positive predictive value 0.85, negative predictive value 0.54, accuracy 0.73). The second-best model was the NCP model (AUC = 0.76). CONCLUSIONS: Combining clinical features with unenhanced CT images of the kidneys seems to be optimal for prediction of WHO/ISUP grade of ccRCC. This noninvasive method may assist in guiding more accurate treatment decisions for ccRCC. ADVANCES IN KNOWLEDGE: This study innovatively employed stability selection for RFs, enhancing model reliability. The CICFs-NCP model's simplicity and efficacy mark a significant advancement, offering a practical tool for clinical decision-making in ccRCC management.

Case of clear-cell oncocytoma of parotid gland and literature review.

Oncocytoma is a benign tumor of the salivary gland. Its incidence is very low and very seldom documen-ted in literature. Clear-cell dominant oncocytoma is even less common. The tumor's clinical symptoms and imaging results are nonspecific, so distinguishing other salivary gland tumors (such as oncocytic carcinoma) from clear-cell renal carcinoma is difficult, possibly leading to misdiagnosis and maltreatment. Here, a case of clear-cell dominant oncocytoma was presented, and the relevant literature was evaluated to investigate the diagnosis and management of clear-cell dominant oncocytoma.

[Retracted] Downregulation of microRNA-206 suppresses clear cell renal carcinoma proliferation and invasion by targeting vascular endothelial growth factor A.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that there appeared to be several instances of overlapping data panels comparing between the Transwell invasion and migration assay images shown in Figs. 2E and 4G, such that data which were intended to show the results from differently performed experiments were apparently derived from a (much) smaller number of original sources. Given the number of cases of overlapping data panels both within and between this pair of figures in the article itself, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal on the basis of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 35: 1778-1786, 2016; DOI: 10.3892/or.2015.4538].

Association of the combined parameters including the frequency of primary cilia, PD-L1, Smoothened protein, membranous ß-catenin and cytoplasmic ß-catenin expression with the outcome of patients with clear cell renal cell carcinoma.

AIMS: The objective of this study was to investigate the association and combined prognostic significance of the PD-L1, Smoothened protein and ß-catenin expressions in patients with clear cell renal cell carcinoma (ccRCC). METHODS: The PD-L1, Smoothened protein and ß-catenin expression were evaluated in 104 ccRCC patients. All studied tumor samples were acquired from nephrectomy specimens of primary tumors and not from biopsies or metastases. An indirect immunohistochemistry using polyclonal rabbit anti-Smoothened antibody, monoclonal mouse anti-human ß-catenin-1 antibody, immunohistochemical assay PD-L1 28-8 pharmDx using monoclonal rabbit anti-PD-L1 antibody and anti-VHL (C- terminal) rabbit antibody was used. Immunohistochemistry was scored semiquantitavely. RESULTS: Median overall survival (OS) was significantly better in patients with lower PD-L1 expression (≤5%), Smoothened protein (SMO) expression (<5%) or cytoplasmic ß-catenin expression (≤75%) than in patients with higher expressions of these biomarkers (P<0.001, P=0.047, and P<0.001, respectively). Membranous ß-catenin showed an opposite effect with its lower expression (≤75%) being associated with longer OS (P=0.020). There was significant association between PD-1 and PD-L1 expression (P=0.007) and significant association of tumor grade (WHO 2016) with membranous ß-catenin (P<0.001), cytoplasmic ß-catenin (P=0.005), pVHL (P=0.042), PD-L1 (P=0.049) and PD-1 (P=0.028) expression. CONCLUSION: The present study provides the first data on the potential association and combined prognostic significance of frequency of primary cilia, PD-L1, Smoothened protein and ß-catenin expression with the outcome in clear cell renal cell carcinoma.

The Value of Dual-Energy Computed Tomography-Based Radiomics in the Evaluation of Interstitial Fibers of Clear Cell Renal Carcinoma.

OBJECTIVE: We investigated the potential of dual-energy computed tomography (DECT) radiomics in assessing cancer-associated fibroblasts in clear cell renal carcinoma (ccRCC). METHODS: A retrospective analysis was conducted on 132 patients with ccRCC. The arterial and venous phase iodine-based material decomposition images (IMDIs), virtual non-contrast images, 70 keV, 100 keV, and 150 keV virtual monoenergetic images, and mixed energy images (MEIs) were obtained from the DECT datasets. On the Radcloud platform, radiomics feature extraction, feature selection, and model establishment were performed. Seven radiomics models were established using the support vector machine. The predictive performance was evaluated by utilizing receiver operating characteristic and the area under the curve (AUC) was calculated. Nomograms were constructed. RESULTS: The combined model demonstrated high efficiency in evaluating pseudocapsule thickness with AUC, specificity, and sensitivity of 0.833, 0.870, and 0.750, respectively in the validation set, surpassing those of other models. The precision, F1-score, and Youden index were also higher for the combined model. For evaluating the number of collagen fibers, the combined model exhibited the highest AUC (0.741) among all models, with a specificity of 0.830 and a sensitivity of 0.330. The AUC in the 150 kv model and IMDI model were slightly lower than those in the combined model (0.728 and 0.710, respectively), with corresponding sensitivity and specificity of 0.560/0.780 and 0.670/0.830. The nomogram exhibited that Rad-score had good prediction efficiency. CONCLUSION: DECT radiomics features have significant value in evaluating the interstitial fibers of ccRCC. The combined model of IMDI + MEI exhibits superior performance in assessing the thickness of the pseudocapsule, while the combined, 150 keV, and IMDI models demonstrate higher efficacy in evaluating collagen fiber number. Radiomics, combined with imaging features and clinical features, has excellent predictive performance. These findings offer crucial support for the clinical diagnosis, treatment, and prognosis of ccRCC and provide valuable insights into the application of DECT.

Proteomic profiling of ovarian clear cell carcinomas identifies prognostic biomarkers for chemotherapy.

Clear cell ovarian carcinoma (CCOC) is a relatively rare subtype of ovarian cancer (OC) with high degree of resistance to standard chemotherapy. Little is known about the underlying molecular mechanisms, and it remains a challenge to predict its prognosis after chemotherapy. Here, we first analyzed the proteome of 35 formalin-fixed paraffin-embedded (FFPE) CCOC tissue specimens from a cohort of 32 patients with CCOC (H1 cohort) and characterized 8697 proteins using data-independent acquisition mass spectrometry (DIA-MS). We then performed proteomic analysis of 28 fresh frozen (FF) CCOC tissue specimens from an independent cohort of 24 patients with CCOC (H2 cohort), leading to the identification of 9409 proteins with DIA-MS. After bioinformatics analysis, we narrowed our focus to 15 proteins significantly correlated with the recurrence free survival (RFS) in both cohorts. These proteins are mainly involved in DNA damage response, extracellular matrix (ECM), and mitochondrial metabolism. Parallel reaction monitoring (PRM)-MS was adopted to validate the prognostic potential of the 15 proteins in the H1 cohort and an independent confirmation cohort (H3 cohort). Interferon-inducible transmembrane protein 1 (IFITM1) was observed as a robust prognostic marker for CCOC in both PRM data and immunohistochemistry (IHC) data. Taken together, this study presents a CCOC proteomic data resource and a single promising protein, IFITM1, which could potentially predict the recurrence and survival of CCOC.

GSDMB: A novel, independent prognostic marker and potential new therapeutic target in clear cell renal cell carcinoma.

Gasdermin (GSDM) family members are involved in numerous biological processes, including pyroptosis, as well as in the initiation and progression of various types of cancer. However, the specific role of GSDM genes in clear cell renal cell carcinoma (ccRCC) has yet to be fully clarified. The present study investigated the differential expression and genetic alterations GSDM genes, their effects on prognosis and immune modulation, and their functional enrichment in ccRCC. Several bioinformatics databases were used, including UALCAN, The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Metascape, Tumor Immune Estimation Resource, GSCALite and cBioPortal. The results revealed that the expression levels of GSDMA, GSDMB, GSDMC and GSDMD were significantly upregulated in cancer tissues compared with those in paracancerous tissues in patients with ccRCC, whereas the expression of DFNB59 exhibited the opposite trend. The results were experimentally validated in patients with ccRCC, and it was confirmed that the expression levels of GSDMA, GSDMB, GSDMC, GSDMD and GSDME (DFNA5) were significantly enhanced, whereas (PJVK, DFNB59) expression was reduced. In addition, elevated GSDMB, GSDMD and DFNA5 expression levels were clearly associated with worse pathological characteristics of ccRCC, including a high pathological stage and high tumor grade. Furthermore, the high expression levels of GSDMB, GSDMC, GSDMD, DFNA5 and PJVK were shown to be associated with worse overall survival (OS) and progression-free interval in patients with ccRCC. Both univariate and multivariate analyses indicated that the expression of GSDMB was independently associated with the OS of patients with ccRCC. Additionally, a high mutation rate of GSDM genes (33%) was observed in patients with ccRCC, and GSDM gene mutations were also significantly associated with a poor OS in patients with ccRCC. Significant associations between GSDM genes and ccRCC immunoprofiling and drug sensitivity were also determined. In conclusion, the findings of the present study indicated that GSDMB, GSDMD and DFNA5 may be considered promising therapeutic agents and potential biomarkers for patients with ccRCC. Furthermore, GSDMB could act as an independent predictor for the OS of patients with ccRCC.

Associations between contrast-enhanced ultrasound features and WHO/ISUP grade of clear cell renal cell carcinoma: a retrospective study.

BACKGROUND: Clear cell renal cell carcinoma (CCRCC) comprises 70%-80% of RCCs. The World Health Organization/International Society of Urology Pathology (WHO/ISUP) classification is the most important prognostic factor for CCRCC. By evaluating the variations of tumor microvascular density, contrast-enhanced ultrasound (CEUS) can noninvasively predict the WHO/ISUP grade of CCRCC, and provide the appropriate treatment plan before clinical operation. METHODS: In this study, we used CEUS features to analyze 116 CCRCC cases and assess the value of correlation between each indicator and CCRCC WHO/ISUP grading. RESULTS: When compared to high-grade (WHO/ISUP grade III/IV) tumors, low-grade (WHO/ISUP grade I/II) tumors had reduced relative peak intensity (ΔPI) (P = 0.021), relative area under the curve (ΔAUC) (P = 0.019). However, the frequency of incomplete pseudocapsule (P = 0.021) was significantly higher in high-grade tumors. A cut-off value of mean diameter > 5.5 cm, ΔPI > 304 × 10-3, ΔAUC > 350 × 10-3 allowed identification of high-grade tumors with an area under the curve (AUC) of 74.6%, 71.7%, 70.7%, respectively (95% confidence interval). CONCLUSIONS: The features of CEUS are effective for differentiating high-grade tumors from low-grade tumors, thus CEUS can be considered an acceptable method for the preoperative assessment of tumor grade.

Radiomics Model for Predicting FOXP3 Expression Level and Survival in Clear Cell Renal Carcinoma.

RATIONALE AND OBJECTIVES: We aimed to evaluate the predictive significance of forkhead box protein 3 (FOXP3) expression levels among individuals with clear cell renal carcinoma (ccRCC) and establish a radiomics model for predicting FOXP3 expression. MATERIALS AND METHODS: 430 patients with ccRCC were included in the gene-based prognostic analyses; 100 samples were used for radiomics feature generation, model development, and evaluation. A gradient boosting machine was employed to model the selected radiomics features. The developed model generated radiomics scores (RS) that predicted FOXP3 expression. The FOXP3 prognostic model combining imaging features was applied for survival and clinical indicator correlation analyses. RESULTS: FOXP3 was highly expressed in patients with ccRCC and served as an independent predictive marker (hazard ratio [HR]=2.357, 95% CI [confidence interval]: 1.582-3.511, p < 0.001). The radiomics model formed by three radiomics characteristics was identified as a strong prognostic indicator of overall survival (OS). The predictive power of the model was commendable (areas under the curve: 0.835 and 0.809 for training and validation sets, respectively). Significant between-group variations in RS distribution were identified, as indicated by gene expression levels (p < 0.05). Disparities were observed in pathological stage, pharmaceutical therapy, and neoplasm status between low and high RS cohorts (p < 0.001). Kaplan-Meier curves revealed a significant correlation between increased RS and decreased OS (p = 0.001), which was also observed in the multivariate analyses (HR=3.411, 95% CI: 1.039-11.196, p = 0.043). CONCLUSION: Prognostic outcome of ccRCC is closely linked to FOXP3 expression level. Computed tomography-based radiomics shows promise for prognostic prediction in ccRCC.

Survival of patients with clear cell renal carcinoma according to number and location of organ-specific metastatic sites.

BACKGROUND: The prognostic significance of number and location of organ-specific metastatic sites in treated metastatic clear cell renal carcinoma (ccmRCC) patients is object of debate. The current study aimed to test the association between number and location of organ-specific metastatic sites and overall survival (OS) in ccmRCC. MATERIALS AND METHODS: Within Surveillance, Epidemiology and End Results database (2010-2018), all ccmRCC patients treated with cytoreductive nephrectomy and/or systemic therapy were identified. Kaplan-Meier plots and Cox regression models focused on: A). number of organ-specific metastatic sites: solitary vs. 2 vs. 3 or more; B). solitary organ-specific metastatic sites (lung vs. bone vs. liver vs. brain); C). combinations of 2 and 3 or more different organ-specific metastatic sites. RESULTS: Of 4,527 patients (median OS: 19 months), 3,054 (67%) harbored solitary organ-specific metastatic sites (27 months) vs. 1,153 (25%) combinations of 2 different organ-specific metastatic sites (12 months) vs. 320 (8%) combinations of 3 or more different organ-specific metastatic sites (7 months). In patients with solitary organ-specific metastatic sites, bone metastases portended the longest median OS (median OS: 31 months) vs. liver metastases portended the shortest median OS (16 months). Both were independent predictors of OS (multivariable hazard ratio, bone: 0.87; liver: 1.21). Median OS was similarly poor in patients with combinations of 2 different organ-specific metastatic sites (9-13 months), regardless of their location. The same pattern applied to patients with combinations of 3 or more different organ-specific metastatic sites (6-7 months). CONCLUSIONS: Solitary organ-specific metastatic sites portend the most favorable OS (16-31 months). Solitary bone metastases yield the longest vs. liver metastases the shortest OS. Invariably poor OS applies to combinations of 2 (9-13 months), as well as 3 or more different organ-specific metastatic sites (6-7 months), regardless of their location.

Circulating tumor cells as a predictor and prognostic tool for metastatic clear cell renal carcinoma: An immunocytochemistry and genomic analysis.

BACKGROUND: Treatment of metastatic clear cell renal carcinoma (mccRCC) has changed dramatically over the past 20 years, without improvement in the development of biomarkers. Recently, circulating tumor cells (CTCs) have been validated as a prognostic and predictive tool for many solid tumors. OBJECTIVE: We evaluated CTCs in blood samples obtained from patients diagnosed with mccRCC. Comparisons of CTC counts, protein expression profiling, and DNA mutants were made in relation to overall survival and progression-free survival. METHODS: CTCs were isolated from 10 mL blood samples using the ISET® system (Isolation by SizE of Tumor Cells; Rarecells, France) and counted. Protein expression was evaluated in immunocytochemistry assays. DNA mutations were identified with next generation sequencing (NGS). RESULTS: Blood samples (10 mL) were collected from 12 patients with mccRCC before the start of first-line systemic therapy, and again 30 and 60 days after the start of treatment. All 12 patients had CTCs detected at baseline (median, 1.5 CTCs/mL; range: 0.25-7.75). Patients with CTC counts greater than the median had two or more metastatic sites and exhibited worse progression-free survival (19.7 months) compared to those with CTC counts less than the median (31.1 months). Disease progression was observed in 7/12 patients during the study. Five of these patients had baseline CTC counts greater than the median, one had higher CTC levels at the second blood collection, and one patient had CTCs present at 1 CTC/mL which positively stained for PD-L1, N-cadherin, VEGF, and SETD2. CTC DNA from six patients with worse outcomes was subjected to NGS. However, no conclusions could be made due to the low variant allele frequencies. CONCLUSION: Detection of CTCs in patients with mccRCC receiving first-line treatment is a feasible tool with prognostic potential since increased numbers of CTCs were found to be associated with metastasis and disease progression.

Sinonasal and Skull Base Metastatic Renal Cell Carcinoma: A Case Series.

Metastatic lesions to the paranasal sinuses and skull base, while rare, carry a poor prognosis. Renal cell carcinoma has been reported in multiple case reports to be one of the most common distant malignancies to spread to the paranasal sinuses; however, it is often unrecognized by physicians, and thus treatment is delayed. To increase awareness of this disease process, we describe three cases of metastatic renal cell carcinoma to the sinonasal cavity, which is the largest case series in the literature to date.

Downregulation of RNA binding protein 47 predicts low survival in patients and promotes the development of renal cell malignancies through RNA stability modification.

RNA binding proteins (RBPs) are crucial for cell function, tissue growth, and disease development in disease or normal physiological processes. RNA binding motif protein 47 (RBM47) has been proven to have anti-tumor effects on many cancers, but its effect is not yet clear in renal cancer. Here, we demonstrated the expression and the prognostic role of RBM47 in public databases and clinical samples of clear cell renal carcinoma (ccRCC) with bioinformatics analysis. The possible mechanism of RBM47 in renal cancer was verified by gene function prediction and in vitro experiments. The results showed that RBM47 was downregulated in renal cancers when compared with control groups. Low RBM47 expression indicated poor prognosis in ccRCC. RBM47 expression in renal cancer cell lines was reduced significantly when compared to normal renal tubular epithelial cells. Epithelial-mesenchymal transition (EMT) and transforming growth factor-ß signaling pathway was associated with RBM47 in ccRCC by Gene set enrichment analysis. RBM47 expression had a positive correlation with e-cadherin, but a negative correlation with snail and vimentin. RBM47 overexpression could repress the migration, invasion activity, and proliferation capacity of renal cancer cells, while RBM47 inhibition could promote the development of the malignant features through EMT signaling by RNA stability modification. Therefore, our results suggest that RBM47, as a new molecular biomarker, may play a key role in the cancer development of ccRCC.