Clear Renal Cell Carcinoma Research Articles

A Review on Systematic Treatment of Clear Cell Renal Cell Carcinoma Using Nivolumab and Cabozantinib

Since the introduction of anti-angiogenic and targeted therapies a decade ago, the management of advanced clear-cell renal cell carcinoma has seen significant advancements. Currently, the standard of care for colorectal cancer includes combinations of tyrosine kinase inhibitors (TKIs) and immunotherapy regimens like cabozantinib and nivolumab. The first-line treatment for RCC involves the combination of the anti-PD-1 monoclonal antibody nivolumab (OPDIVO®) and the multi-targeted TKI cabozantinib (Cabometyx®). Throughout the trial, the combination of cabozantinib and nivolumab consistently led to an enhanced health-related quality of life. Cabozantinib is used in the treatment of kidney cancer, hepatocellular carcinoma, and renal cell carcinoma. Nivolumab is typically employed when anti-angiogenic therapy proves ineffective. The combination of cabozantinib plus nivolumab, involving medications like sunitinib, ipilimumab, lenvatinib, and axtinib, is primarily utilized for its efficacy and survival benefits. The present review describes cabozantinib and nivolumab which are used for cancer treatment. This review helps people who are suffering from clear cell renal cell carcinoma.

Aristolochic acid-related renal cell carcinoma exhibits a distinct tumor-immune microenvironment favoring response to immune checkpoint blockade.

Immune checkpoint blockade (ICB) is currently the standard of care for metastatic renal cell carcinoma (RCC), but treatment responses remain unpredictable. Aristolochic acid (AA), a prevalent supplement additive in Taiwan, has been associated with RCC and induces signature mutations, although its effect on the tumor-immune microenvironment (TIME) is unclear. We aimed to investigate the immune profile of AA-positive RCCs and explore its potential role as a susceptible candidate for ICB. Tissue samples from 22 patients with clear cell RCC (ccRCC) were collected for whole-exome sequencing to determine the genetic features and AA mutational signature (the discovery cohort). The corresponding RNA was sent for NanoString PanCancer IO 360 gene expression analysis to explore the immunological features. The formalin-fixed, parafilm-embedded slides of ccRCCs were sent for multiplex immunohistochemistry/immunofluorescence stain using Vectra system to evaluate the TIME. Tissues from two patients with metastatic RCC demonstrating complete response to ICB were sent for studies to validate the findings (the index patients). The results showed that AA mutational signatures with high tumor mutational burden (TMB) were present in 31.81% of the tumors in the discovery cohort. Three distinct clusters were observed through NanoString analysis. Clusters 1 and 3 were composed mainly of AA-positive RCCs. Cluster 3 RCCs exhibited higher tumor inflammation signature scores and higher immune cell type scores. Vectra analysis revealed a higher percentage of CD15+ and BATF3+ cells in cluster 1, whereas the percentage of CD8+ cells was potentially higher in cluster 3. Strong AA mutational signatures were found in the tumors of two index patients, and both were grouped to cluster 3. In conclusion, AA may induce higher TMB and alter the immune microenvironment in RCCs, which makes the tumors more susceptible to ICB. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Identification of Cuproptosis-Associated Prognostic Gene Expression Signatures from 20 Tumor Types.

We investigated the mRNA expression of 124 cuproptosis-associated genes in 7489 biopsies from 20 different tumor types of The Cancer Genome Atlas (TCGA). The KM plotter algorithm has been used to calculate Kaplan-Meier statistics and false discovery rate (FDR) corrections. Interaction networks have been generated using Ingenuity Pathway Analysis (IPA). High mRNA expression of 63 out of 124 genes significantly correlated with shorter survival times of cancer patients across all 20 tumor types. IPA analyses revealed that their gene products were interconnected in canonical pathways (e.g., cancer, cell death, cell cycle, cell signaling). Four tumor entities showed a higher accumulation of genes than the other cancer types, i.e., renal clear cell carcinoma (n = 21), renal papillary carcinoma (n = 13), kidney hepatocellular carcinoma (n = 13), and lung adenocarcinoma (n = 9). These gene clusters may serve as prognostic signatures for patient survival. These signatures were also of prognostic value for tumors with high mutational rates and neoantigen loads. Cuproptosis is of prognostic significance for the survival of cancer patients. The identification of specific gene signatures deserves further exploration for their clinical utility in routine diagnostics.

Molecular signature of immune-related new survival predictions for subtype of renal cell carcinomas.

Kidney renal papillary cell carcinoma (KIRP), kidney chromophobe (KICH), and kidney renal clear cell carcinoma (KIRC) are three most common subtypes of renal cell carcinomas (RCC), and its development is a multifaceted process that intricately involves the interplay of numerous genes. Despite recent advances in research on renal cell carcinoma, the prognosis of KIRC patients remains dismal. Therefore, there is an urgent need to explore new prognostic biomarkers and treatment strategies to help clinicians choose more effective treatment methods and accurately predict long-term efficacy. Our study aimed to systematically evaluate the gene expression profiles of three RCC subtypes, especially KIRC, and to identify survival-related biomarker. In our present study, we systematically evaluate the genes expression profile difference among three subtypes of RCC, and identify the survival-related key genes signature based on GEPIA2. GeneMANIA was used to identify the functionality-related differentially expressed genes (DEGs). Furthermore, focusing on KIRC, we intersected functionality-related and survival-related DEGs based on two datasets. We ascertained five DEGs (ANK3, FREM2, KIF13B, MPP7 and SOX6) as key survival-related genes in KIRC. High levels of these five DEGs expressions were strongly associated with favorable prognosis, but not correlated to metastasis. Downregulation of these five DEGs expressions was closely associated with immunomodulators, chemokines, and infiltrating levels of different immune cells, which indicated that these five DEGs were key immune-related novel prognostic biomarkers for KIRC. The five identified DEGs serve as potential novel prognostic biomarkers for KIRC. However, the crucial factors that lead to the downregulation and functional inactivation of these five key genes need to be explored in future studies.

PIEZO1 mediates matrix stiffness-induced tumor progression in kidney renal clear cell carcinoma by activating the Ca2+/Calpain/YAP pathway

ObjectiveThe significance of physical factors in the onset and progression of tumors has been increasingly substantiated by a multitude of studies. The extracellular matrix, a pivotal component of the tumor microenvironment, has been the subject of extensive investigation in connection with the advancement of KIRC (Kidney Renal Clear Cell Carcinoma) in recent years. PIEZO1, a mechanosensitive ion channel, has been recognized as a modulator of diverse physiological processes. Nonetheless, the precise function of PIEZO1 as a transducer of mechanical stimuli in KIRC remains poorly elucidated. MethodsA bioinformatics analysis was conducted using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) to explore the correlation between matrix stiffness indicators, such as COL1A1 and LOX mRNA levels, and KIRC prognosis. Expression patterns of mechanosensitive ion channels, particularly PIEZO1, were examined. Collagen-coated polyacrylamide hydrogel models were utilized to simulate varying stiffness environments and study their effects on KIRC cell behavior in vitro. Functional experiments, including PIEZO1 knockdown and overexpression, were performed to investigate the molecular mechanisms underlying matrix stiffness-induced cellular changes. Interventions in the Ca2+/Calpain/YAP Pathway were conducted to evaluate their effects on cell growth, EMT, and stemness characteristics. ResultsOur findings indicate a significant correlation between matrix stiffness and the prognosis of KIRC patients. It is observed that higher mechanical stiffness can facilitate the growth and metastasis of KIRC cells. Notably, we have also observed that the deficiency of PIEZO1 hinders the proliferation, EMT, and stemness characteristics of KIRC cells induced by a stiff matrix. Our study suggests that PIEZO1 plays a crucial role in mediating KIRC growth and metastasis through the activation of the Ca2+/Calpain/YAP Pathway. ConclusionThis study elucidates a novel mechanism through which the activation of PIEZO1 leads to calcium influx, subsequent calpain activation, and YAP nuclear translocation, thereby contributing to the progression of KIRC driven by matrix stiffness.

The pan-cancer landscape of crosstalk between leukocyte transendothelial migration-related genes and tumor microenvironment relevant to prognosis and immunotherapy response.

Leukocyte transendothelial migration-related genes (LTEMGs) play a crucial role in the immune response and have been extensively studied in various pathological conditions, including inflammation, infection, and cancer. In recent years, increasing attention has been given to understanding the biological mechanisms of LTEMGs in the context of tumor progression and metastasis. The potential function of LTEMGs in cancer progression remains unclear. The aim of this study is to systematically delineate the relationship between LTEMGs and tumor prognosis and immune microenvironment at the pan-cancer level, providing new biomarkers for personalized immunotherapy. The gene alteration, messenger RNA (mRNA) expression, and prognostic value of LTEMGs in pan-cancer were evaluated using Bulk and single-cell RNA (scRNA) sequence data. The LTEMGs score was calculated by R package "GSVA". The association of LTEMGs score with tumor microenvironment and immunotherapy response were deeply explored. We assessed the mRNA expression of 114 LTEMGs across various cancers, finding significant upregulation in acute myeloid leukemia (LAML) and pancreatic adenocarcinoma (PAAD). Prognostic analysis indicated most LTEMGs were risk factors in low-grade glioma (LGG), PAAD, uveal melanoma (UVM), and LAML. The LTEMGs score, highest in kidney renal clear cell carcinoma (KIRC) and lowest in UVM, was higher in tumor tissues compared to normal tissues in several cancers. The score was a risk factor for overall survival (OS) in LGG, UVM, and others, but protective in KIRC and some others. LTEMGs score correlated positively with Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling, apoptosis, and immune responses. It also correlated with immune and stromal scores, and immune-related pathways. Higher LTEMGs score was linked to greater immune cell infiltration and poorer immunotherapy outcomes. Single-cell analysis revealed higher LTEMGs score in endothelial and monocyte cells, consistent with reduced immunotherapy responsiveness. Our results reveal that LTEMGs are closely associated with tumor microenvironment. Patients with high LTEMGs score might be resistant to immunotherapy.

ERBB2 is a potential diagnostic and prognostic biomarker in renal clear cell carcinoma

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways “BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation” and “AMAN pathway”. In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Construction and experimental verification of a novel nine-glycosylation-related gene prognostic risk model for clear cell renal carcinoma

ObjectivePatients with clear cell renal carcinoma (ccRCC) typically have poor prognosis. Glycosylation modification plays an important role in ccRCC. This study aimed to develop a novel signature for predicting ccRCC prognosis based on glycosylation-related genes (GRGs). MethodsDifferentially expressed GRGs (DE_GRGs) were identified using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus and used for constructing the risk model. The function of key genes was validated. ResultsTwenty-two DE_GRGs were intersected between GSE53757 and TCGA. Patients with ccRCC were divided into two clusters based on the expression profile of these DE_GRGs. Significant differences in the infiltration of 10 immune cell types were observed between two subclusters. Subsequently, the prognostic signatures of nine DE_GRGs (CHST9, COLGALT1, FUT3, FUT6, HS3ST2, POMGNT2, ST8SIA4, UGT3A1, and UGT8) were established. Patients in the high-risk group showed a poorer prognosis relative to the low-risk group. According to univariate and multivariate Cox regression analyses, the risk score, stage, and grade could be independent prognostic factors. A nomogram incorporating information on gender, age, risk group, TNM stage, and clinical stage showed accurate prediction in the survival probability. Except for CHST9, HS3ST2, and ST8SIA4, expression patterns of the remaining 6 DE_GRGs in Caki-1and 786-O cells were confirmed by quantitative real-time PCR. FUT6 overexpression resulted in the inhibition of proliferation, migration, and invasion of ccRCC cells. ConclusionThis study established a nine-DE_GRG-based prognostic signature, which independently predicted ccRCC prognosis. This finding emphasizes that GRGs are stratification factors for the precise prognosis of ccRCC.

4 Oral: Casdatifan in patients (pts) with previously treated clear cell renal cell cancer (ccRCC) and other solid tumors; preliminary results from ARC- 20: A phase 1, open-label dose-escalation and expansion study

4 Oral: Casdatifan in patients (pts) with previously treated clear cell renal cell cancer (ccRCC) and other solid tumors; preliminary results from ARC- 20: A phase 1, open-label dose-escalation and expansion study

Expression analysis, molecular docking and molecular dynamics simulations to identify potential BTK inhibitors: strategy for targeting pan-cancer

ABSTRACT Bruton's Tyrosine Kinase (BTK), a soluble tyrosine kinase plays an essential role in the growth, development, and signalling of B cells. It is a non-receptor kinase that is crucial for leukemic cell survival, proliferation, and oncogenic signalling in many B cell malignancies. The enhanced metastasis caused by BTK expression may be reduced by BTK inhibitors, which also have powerful therapeutic effects. The goal of the study is to identify potential inhibitors which have good binding affinity with BTK. The current study also aims to investigate the expression pattern and the prognostic significance of BTK across all cancer types. Interestingly, it was found that BTK was highly overexpressed in numerous cancer types including; clear cell renal carcinoma, glioblastoma, head and neck, liver and breast cancer. BTK was found to reduce the relapse-free and overall survival rate. Furthermore, using in silico approach two structural analogues of Pirtobrutinib namely; 163207918 and 129269825 that bind to BTK with higher affinity were identified. Using drug-likeness analysis the therapeutic possibility of screened Pirtobrutinib analogues were evaluated. The Molecular docking and dynamic analysis revealed that the new Pirtobrutinib analogues could be potent inhibitors with higher binding affinity and stability in comparison with the parent compound. In conclusion, after preclinical and clinical research, the identified analogues may open the door for their prospective use in cancer therapy.

Identification of key ferroptosis genes and subtypes in kidney renal clear cell carcinoma

Tumour immunity is highly important for the occurrence and development of tumours, and many cancers are resistant to ferroptosis. This study aims to explore the relationship between ferroptosis-related genes (FRGs) and the immunological characteristics of kidney renal clear cell carcinoma (KIRC). We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman’s correlation analysis. Based on the expression of CD44 and GLRX5, the consensus clustering algorithm was used to classify the TCGA-KIRC samples into two clusters. A nomogram was constructed to evaluate the prognosis of KIRC patients. ESTIMATE, CIBERSORT, and single-sample gene set enrichment analysis (ssGSEA) were performed to evaluate immune infiltration between the two clusters. A weighted gene co-expression network analysis (WGCNA) was used to identify the most relevant genes to the clusters and immunity. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The external dataset GSE53757 was used to validate the immunological features between the two clusters. Cluster 2 patients had more active immune infiltration and might be more sensitive to immunotherapy; Cluster 2 patients also had a worse prognosis and might be at a more advanced stage of KIRC. We identified key ferroptosis-related genes and subgroups involved in the immune infiltration of KIRC, which is highly important for exploring the molecular mechanisms and treatments of KIRC.

Comprehensive analysis of the potential biological significance of CCL5 in pan-cancer prognosis and immunotherapy

C-C chemokine ligand 5 (CCL5) plays a crucial role in the advancement of human cancer. Nevertheless, little is known about the multi-omics characterisation of CCL5 and its significance for the immune microenvironment and prognosis of tumor patients. The basal expression levels of the CCL5 gene in normal human tissues, aberrant expression in disease, genomic alterations, prognostic roles, pathway enrichment, immune microenvironment, association with immune checkpoints, drug sensitivity, and the ability to predict patients’ immunotherapeutic response to immune checkpoint inhibitors (ICIs) and small molecule drugs were all thoroughly analyzed using data gathered from 33 cancers. Lastly, we were able to validate CCL5’s involvement in renal clear cell carcinoma by experimental means. We discovered that CCL5 has distinct expression patterns and a diagnostic biomarker significance in cancer. Furthermore, we discovered that CCL5 is essential for both the tumor microenvironment and pan-cancer. TMB and MSI are two frequent immunological checkpoints that are significantly correlated with CCL5, and patients who express high levels of CCL5 have stronger immunotherapeutic response and a better prognosis after immunotherapy. Eventually, molecular docking was used to find small molecule inhibitors that can specifically target CCL5. Ultimately, it was shown that CCL5 knockdown impeded renal clear cell carcinoma cells’ ability to proliferate and invade. Our findings demonstrate the significant potential of CCL5 as an immunotherapeutic response biomarker and prognostic indicator, which may pave the way for more studies on the mechanism of tumor infiltration and CCL5’s potential therapeutic applications in cancer.

Is fat quantification based on proton density fat fraction useful for differentiating renal tumor types?

This study retrospectively assessed the diagnostic accuracy of fat quantification based on proton density fat fraction (PDFF) for differentiating renal tumors. In this retrospective study, 98 histologically confirmed clear cell renal cell carcinomas (ccRCCs), 35 papillary renal cell carcinomas (pRCCs), 14 renal oncocytomas, 16 chromophobe renal cell carcinomas (chRCCs), 10 lymphomas, 19 uroepithelial tumors, 10 lipid-poor angiomyolipomas (AMLs), and 25 lipid-rich AMLs were identified in 226 patients (127 males and 99 females) over 5years. All patients underwent multiparametric kidney MRI. The MRI protocol included an axial plane and a volumetric 3D fat fraction sequence known as mDIXON-Quant for PDFF measurement. Demographic data were recorded, and PDFF values were independently reviewed by two radiologists blinded to pathologic results. MRI examinations were performed using a 1.5T system. MRI-PDFF measurements were obtained from the solid parts of all renal tumors. Fat quantification was performed using a standard region of interest for each tumor, compared to histopathological diagnoses. Sensitivity and specificity analyses were performed to calculate the diagnostic accuracy for each histopathological tumor type. Nonparametric variables were compared among the subgroups using the Kruskal-Wallis H test and Mann Whitney U test. P-values < 0.05 were considered statistically significant. In all, 102 patients underwent partial nephrectomy, 70 patients underwent radical nephrectomy, and the remaining 54 had biopsies. Patient age (mean: 58.11years; range: 18-87years) and tumor size (mean: 29.5mm; range: 14-147mm) did not significantly differ across groups. All measurements exhibited good interobserver agreement. The mean ccRCC MRI-PDFF was 12.6 ± 5.06% (range: 11.58-13.61%), the mean pRCC MRI-PDFF was 2.72 ± 2.42% (range: 2.12-3.32%), and the mean chRCC MRI-PDFF was 1.8 ± 1.4% (range: 1.09-2.5%). Clear cell RCCs presented a significantly higher fat ratio than other RCC types, uroepithelial tumors, lymphomas, and lipid-poor AMLs (p < 0.05). Lipid-rich AMLs demonstrated a very high fat ratio. MRI-PDFF facilitated accurate differentiation of ccRCCs from other renal tumors with high sensitivity and specificity.

Exploring the Effect of Fidgetin-Like 1 on Colorectal Cancer Through Tissue Chip and In Vitro Experiments

Fidgetin-like 1 (FIGNL1) is extensively overexpressed in a variety of cancers. It facilitates non‑small cell lung cancer tumor cell proliferation and hepatocellular carcinoma formation due to abnormal DNA repair. Clinically relevant data indicates that its high expression is linked with the poor prognosis of patients with renal clear-cell carcinoma, low-grade gliomas, and hepatocellular carcinoma. Nevertheless, the scope of FIGNL1’s involvement in cancer, particularly colorectal cancer (CRC), remains unclear. To investigate the function of FIGNL1 in CRC. Cell culture study. The TCGA database and immunohistochemistry analysis were employed to investigate FIGNL1 expression in CRC tissue. A cell viability assay was performed using the Cell Counting Kit-8. The cell migration and invasion were evaluated using the transwell assay. Small interfering RNA (siRNA) transfection was conducted to knockdown FIGNL1 expression. Infection with FIGNL1 overexpression lentivirus was performed to promote FIGNL1 overexpression. The STRING database was employed for predicting protein interaction. FIGNL1 was substantially upregulated in human CRC tissues and was associated with TNM stages and lymph node metastasis in patients. The inhibition of CRC cell proliferation, migration, and invasion in Caco-2 cells was achieved by silencing FIGNL1 using siRNA. Additional investigations suggested that FIGNL1 overexpression could promote CRC cell proliferation, migration, and invasion via P38 signaling pathway activation in Colo-205 cells. Subsequent experiments demonstrated that FIGNL1-mediated P38 phosphorylation was contingent upon SPIDR interaction. These results implied that FIGNL1 was a potential anticancer drug target, which also offered a novel strategy for future CRC treatment.

Tumor microbiota of renal cell carcinoma affects clinical prognosis by influencing the tumor immune microenvironment

Despite reported influences of the intratumoral microbiome on cancer progression, its role in this subtype remains unclear. This study aimed to characterize the microbial landscape and signatures of kidney renal clear cell carcinoma using RNA-Seq data from The Cancer Genome Atlas. Following microbial decontamination, differential microbial analysis was conducted between tumorous and adjacent non-tumorous samples. Compared to non-tumorous samples, tumorous microbiota exhibited reduced α and β diversity and distinct phylum-level communities. Differential microbial analysis between patients exhibiting long and short overall survival revealed ten significant differential microbial genera, with six genera correlating with a positive prognosis (Plasmodium, Babesia, Toxoplasma, Cytobacillus, Alicyclobacillus, Verrucomicrobium) and four with a negative prognosis (Colletotrichum, Leuconostoc, Gluconobacter, and Parabacteroides). Employing Cox regression analysis and support vector machines, a prognosis-related microbiome risk signature was developed, achieving an AUC of 0.809. Based on this risk signature, two microbiome-based subtypes were found to be significantly associated with distinct clinical prognoses and immune microenvironments. These findings were corroborated by significant correlations between prognostic-relevant microorganisms and 30 immune-related differentially expressed genes. Specifically, microbial genera associated with a negative prognosis were linked to a pro-tumor acute inflammatory immune response, whereas genera related to a positive prognosis were associated with an anti-tumor adaptive immune response. In conclusion, microbiome-based subtyping revealed correlations between tumor microbiome, clinical prognosis, and tumor microenvironment, indicating intratumoral microbiota as a promising prognostic biomarker for kidney renal clear cell carcinoma.

Development and validation of a CT based radiomics nomogram for preoperative prediction of ISUP/WHO grading in renal clear cell carcinoma

Development and validation of a CT based radiomics nomogram for preoperative prediction of ISUP/WHO grading in renal clear cell carcinoma

Surgical resection and survival of clear cell renal cancer metastases to the pancreas

Surgical resection and survival of clear cell renal cancer metastases to the pancreas

PET/CT with 18F-PSMA-1007 in Diagnostics of Metastatic Lesions of Clear-Cell Renal Cell Carcinoma in Comparison with 18F-FDG: Prospective Study

PET/CT with 18F-PSMA-1007 in Diagnostics of Metastatic Lesions of Clear-Cell Renal Cell Carcinoma in Comparison with 18F-FDG: Prospective Study

Screening miRNAs to Hinder the Tumorigenesis of Renal Clear Cell Carcinoma Associated with KDR Expression.

This study delved into the role of Kinase Insert Domain Receptor (KDR) and its associated miRNAs in renal cell carcinoma through an extensive computational analysis. The potential of our findings to guide future research in this area is significant. Our methods, which included the use of UALCAN and GEPIA2 databases, as well as miRDB, MirDIP, miRNet v2.0, miRTargetLink, MiEAA v2.1, TarBase v8.0, INTERNET, and miRTarBass, were instrumental in identifying the regulation of miRNA associated with KDR expression. The predicted miRNA was validated with the TCGA-KIRC patients' samples by implementing CancerMIRNome. The TargetScanHuman v8.0 was implemented to identify the associations between human miRNAs and KDR. A Patch Dock server analyzed the interactions between hsa-miR-200b-3p-KDR and hsa-miR-200b-3p with KDR. The KDR expression rate was investigated in the Kidney Renal Cell Carcinoma (KIRC) samples, and adjacent normal tissues revealed that the expression rate was significantly higher than the normal samples, which was evident from the strong statistical significance (P = 1.63e-12). Likely, the KDR ex-pression rate was estimated as high at tumor grade 1 and gradually decreased till the metastasis grade, reducing the survival rate of the KIRC patients. To identify these signals early, we predicted a miRNA that could trigger the expression of KDR. Furthermore, we uncovered the potential associations between miR-200c-3p expressions by regulating KDR towards the progression of KIRC. Upon examining the outcome, it became evident that miR-200c-3p was significantly down-regulated in KIRC compared to the normal samples. Moreover, the negative correlation was obtained for hsa-miR-200c-3p (R = - 0.276) along with the KDR expression describing that the increased rate of hsa-miR-200c-3p might reduce the KDR expression rate, which may suppress the KIRC initiation or progres-sion. The in-silico analysis indicated that the significant increase in KDR expression during the initiation of KIRC could serve as an early diagnostic marker. Moreover, KDR could be utilized to identify advancements in KIRC stages. Additionally, hsa-miR-200c-3p was identified as a potential regulator capable of downregulating and upregulating KDR expression among the 24 miRNAs screened. This find-ing holds promise for future research endeavors. Concurrent administration of the FDA-approved 5-fluor-ouracil with KIRC drugs, such as sorafenib, zidovudine, and everolimus, may have the potential to en-hance the therapeutic efficacy in downregulating hsa-miR-200c-3p. However, further in vitro studies are imperative to validate these findings and gain a comprehensive understanding of the intricate regulatory interplay involving hsa-miR-200c-3p, KDR, 5-fluorouracil, and other FDA-approved drugs for the treat-ment of KIRC. This will facilitate the identification of KIRC stage progression and its underlying pre-ventative mechanisms.

Renal Findings in Patients with Thalassemia at Abdominal Ultrasound: Should We Still Talk about "Incidentalomas"? Results of a Long-Term Follow-Up.

We retrospectively collected all ultrasound imaging data of our thalassemia patients over a period of 10 years with the aim of assessing the prevalence and the risk factors of renal stones and cysts. Moreover, we assessed the incidence of renal-cell carcinoma (RCC) among thalassemia patients (133 with thalassemia major (TM) and 157 with thalassemia intermedia (TI)) and its association with demographic and clinical findings. Renal stones were detected in 15.2% of patients. In the multivariable Cox regression analysis, the independent predictors were blood consumption, splenectomy, and proteinuria. Renal cysts were detected in 18.4% of patients. In the multivariable analysis, age emerged as the only independent predictor. After the first detection, 35% of the patients showed changes in the number, size, or grading of renal cysts. During the study period, the crude incidence rate of RCC was 75.9 cases per 100,000 person-years. The most frequent histological subtype (80%) included clear-cell RCC. In total, 80% of patients with RCC had TM and all were positive for hepatitis C virus antibodies. Thalassemia patients are significantly affected by asymptomatic renal diseases such as stones, cysts, and cancer, suggesting the need for regular screening by imaging.