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Clear cell renal cell carcinoma (ccRCC), a predominant form of urinary malignancy, requires the identification of reliable biomarkers to enhance both prognostic outcomes and therapeutic developments specific to ccRCC. NSUN5, a member of the NOL1/NOP2/SUN domain (NSUN) family, plays a critical role in RNA stabilization and exhibits widespread expression across various tumor types. However, the exact function of NSUN5 in ccRCC remains insufficiently understood. Data were collated from cohorts of ccRCC patients who underwent nephrectomy, including those from the Cancer Genome Atlas (TCGA) and the Sun Yat-sen University Cancer Center (SYSUCC), to evaluate the clinical relevance of NSUN5. Integrative models based on NSUN5 expression were subsequently developed to predict the prognosis of ccRCC within the TCGA and SYSUCC cohorts. Furthermore, the impact of NSUN5 on RCC cells and its association with cellular senescence were corroborated through in vitro experimental analyses. NSUN5 exhibited elevated expression in both ccRCC patients and renal cancer cell lines, whose upregulation significantly correlated with age, tumor size, TNM stage, WHO/International Society of Urological Pathology (ISUP) grade, presence of necrosis, and a poor prognosis. An accessible nomogram, incorporating NSUN5 along with various clinicopathological parameters, was adept at predicting outcomes for ccRCC patients. Additionally, in vitro findings indicated that reduced expression of NSUN5 enhanced tumor cell senescence and simultaneously inhibiting cell proliferation and migration. These observations suggest that elevated NSUN5 expression is linked to poorer overall survival (OS) and progression-free survival (PFS), positioning NSUN5 as a viable diagnostic and prognostic biomarker in ccRCC., Competing Interests: Declarations Competing interests The authors have no relevant financial or non-financial interests to disclose. The authors declare no competing interests. Ethical approval This study has been approved by the Institute Research Medical Ethics Committee of Sun Yat-sen University Cancer Center. (Document: SL-B2022-288-01) Consent to participate Our research is not involving human subjects, so informed consent was not written. Consent to publish Our manuscript contains any individual person’s data in any form., (© 2024. The Author(s).)

Renal cell carcinoma (RCC) represents a significant portion of genitourinary cancers, marked by challenging prognosis and high metastasis rates. Immunotherapy has been applied in managing advanced renal cell carcinoma, but the therapeutic outcomes are unsatisfactory. In this study, we order to construct a Janus kinase/signal transduction and activator transcriptional (JAK/STAT)-related signature linked to kidney patient outcomes for better predicting the efficacy to immune checkpoint inhibitors (ICIs) and to provide guidance for effective combination therapy. We screened 25 differentially expressed genes (DEGs) that exhibited high expression in RCC samples and were enriched in the JAK-STAT signaling pathway. Among these genes, 11 key genes were identified and correlated with the expectation of Kidney Clear Cell Carcinoma (KIRC) patients and all these genes was significantly elevated in RCC tumor tissues and cancer cells compared to para-cancer tissues and normal renal cells. Utilizing these 11 genes, we divided RCC patients into high-risk and low-risk groups. We found a clear correlation between the clinicopathologic factors of KIRC patients and the JAK-STAT-related risk score. And the IHC results shown that the JAK3 and STAT4 expression of tumor was significantly higher than normal tissue in RCC patients, the level of JAK3 and STAT4 was positively related to the T stage of RCC patients. In addition, high-risk patients had a poorer prognosis and greater protumor immune cell infiltration, and benefitted less from immunotherapy than did low-risk patients. Furthermore, the JAK-STAT-related risk score can predict disease-free survival (DFS) in RCC patients according to the nomogram, which constructed in combination with other clinical features such as age, TNM-staging and stage. Our study demonstrated the JAK-STAT signaling pathway's important regulatory function in RCC tumor immunity. This insight not only enhances our ability to accurately predict the survival rate of RCC patients, but also underscores a potential therapeutic alternative for RCC, involving the combined targeting of the JAK-STAT pathway and immune checkpoints., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

dCTP pyrophosphatase 1 (DCTPP1) is widely expressed in tumors and the immune system and plays a critical role in human cancer progression. However, multi-omics characterization of DCTPP1 and its role in prognosis and immune microenvironment of tumor patients has not been explored. We collected data from 33 cancers and comprehensively analyzed the aberrant expression, prognostic role, pathway enrichment, immune microenvironment, and association with drug sensitivity of DCTPP1 in cancers, as well as the prediction of patients' immunotherapeutic response to ICIs and targeted small molecule drugs. Finally, we experimentally confirmed the role of DCTPP1 in renal clear cell carcinoma. We discovered that DCTPP1 has a differentiable expression and a diagnostic biomarker significance in cancer. Additionally, we discovered that DCTPP1 is important for the tumor microenvironment and pan-cancer. TMB and MSI are frequent immunological checkpoints that are significantly correlated with DCTPP1 expression. Patients who express high levels of DCTPP1 have greater rates of survival and therapeutic response following immunotherapy. Ultimately, it was discovered that renal clear cell carcinoma cells' invasion and proliferation were suppressed by DCTPP1 knockdown. Our findings demonstrate the significant potential of DCTPP1 as a biomarker for prognosis and immunotherapeutic response, which may pave the way for more investigation into the mechanism of tumor infiltration and DCTPP1's potential for cancer therapy., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The present study investigated the Zinc finger BED-type containing 3 (ZBED3) mRNA expression levels, diagnostic and prognostic values, co-expressed and differentially expressed genes, immune infiltration, and functional enrichment analysis in patients with kidney renal clear cell carcinoma (KIRC) using various public databases such as The Cancer Genome Atlas, Genotype-Tissue Expression Project, LinkedOmics, Gene Set Enrichment Analysis databases, and the Xiantao academic tool. Through extensive data mining, our study revealed differential expression of ZBED3 in various tumor and paired normal tissues. Specifically, ZBED3 expression was found to be significantly decreased in KIRC, particularly in advanced pathologic stages and histologic grades, when compared to corresponding control tissues. Our analysis revealed that the overexpression of ZBED3 is associated with a favorable overall survival outcome in KIRC patients. Moreover, functional enrichment analysis identified key pathways related to inflammation response and DNA methylation of ZBED3 in KIRC. Additionally, our findings suggest that the upregulation of ZBED3 leads to the inhibition of cell proliferation by modulating cell-cycle progression in KIRC cell lines. Taken together, these results suggest that ZBED3 may serve as a promising biomarker and prognostic indicator for individuals diagnosed with KIRC., (© 2024. The Author(s).)

Objectives: To analyze the diagnostic and prognostic potential of the BOLA gene family in kidney renal clear cell carcinoma (KIRC)., Methods: This study is an observational study. The whole study was carried out at Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia from January to November 2023. As it involves in silico and in vitro methods, ethical consent was not required. Various in silico and molecular experimental techniques were employed in this study., Results: Significant up-regulation and hypomethylation of BOLA1, BOLA2, and BOLA3 were observed across 12 KIRC cell lines. Retrospective analysis of the cancer genome atlas program (TCGA)-KIRC cohorts confirmed hypomethylation of these genes in KIRC tissues. The cBioPortal analysis showed minimal genetic alterations, with amplification being the most common. Kaplan-Meier plotter data revealed that high BOLA1, BOLA2, and BOLA3 expression correlated with shorter overall survival and relapse-free survival in KIRC. Tumor-immune system interactions database analysis linked BOLA1 expression to immune and molecular subtypes. Gene silencing of BOLA1, BOLA2, and BOLA3 in 786-0 cells reduced cell growth and proliferation, enhancing wound healing capacity., Conclusion: BOLA genes may serve as diagnostic and prognostic markers in KIRC, offering insights into therapeutic targets and disease progression., (Copyright: © Saudi Medical Journal.)

Bladder cancer (BCa) and renal cell carcinoma (RCC) are prevalent urologic malignancies (UM) characterized by high morbidity and frequent recurrence. Current diagnostic approaches, often invasive, often indicate an advanced disease stage. And the complex tumor microenvironment often promotes tumor progression and induces resistance to chemotherapy. Current diagnostic and therapeutic modalities often fail to achieve satisfactory outcomes for patients. Exosomes transport diverse cargoes, including cytokines, proteins, lipids, non-coding RNAs, and microRNAs, crucial for intercellular communication. Exosomes have shown potential as biomarkers for UM, participating in tumor progression, especially within the tumor microenvironment (TME), including tumor cell apoptosis, proliferation, migration, invasion, depletion of immune cell function, epithelial-mesenchymal transition (EMT), angiogenesis, and more.In this review, we summarize research advances related to exosomes in UM, focusing on the role of exosomes as biomarkers in bladder and renal cancer, highlighting their significance within the TME., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background/aim: Renal cell carcinoma (RCC) is highly heterogeneous, with distinct patient management between clear cell RCC (ccRCC) and non-ccRCC groups. Previous bioinformatics and machine learning techniques identified fatty acid binding protein 7 (FABP7) as a potential ccRCC biomarker. However, FABP7 expression studies between ccRCC and non-ccRCC were incomplete. This study aimed to assess FABP7 as a biomarker for distinguishing between ccRCC and non-ccRCC tissue samples., Patients and Methods: FABP7 expression was evaluated via immunohistochemical staining in 58 RCC cases, including 43 ccRCC and 15 non-ccRCC cases. Staining results were interpreted using H-scores; scores above the cut-off were deemed positive. The correlation between FABP7 expression and clinicopathological RCC features was investigated., Results: FABP7 positivity was 48.8% in ccRCC and only 13.3% in non-ccRCC cases, with weak positivity in non-ccRCC tissues. FABP7 expression significantly differed between ccRCC and non-ccRCC (p<0.05). This finding was confirmed in a TCGA dataset. However, FABP7 expression was not correlated with other RCC clinicopathological features in our dataset. TCGA results linked FABP7 expression to tumor stage and disease-free survival in patients with ccRCC., Conclusion: This study preliminarily evaluated FABP7 as a differential diagnostic biomarker in RCC subtyping, showing higher expression in ccRCC than non-ccRCC. FABP7 may serve as a potential diagnostic and prognostic biomarker for ccRCC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Renal cell carcinoma (RCC) is one of the most frequent urological cancers globally that has a good prognosis in the early tumor stages. However, there is a poor prognosis in metastatic RCC patients. Therefore, it is needed to evaluate the molecular biology of RCC progression to introduce the efficient diagnostic and therapeutic markers in these patients. Long non-coding RNAs (lncRNAs) have key roles in regulation of molecular mechanisms during RCC progression. In the present study, we assessed the levels of LINC00365 expressions in RCC patients to suggest that as a tumor marker in these patients., Methods: Fifty fresh RCC tumor tissues and their normal margins were collected to assess the levels of LINC00365 expressions and probable correlations with clinicopathological features of RCC patients., Results: There was significant LINC00365 up regulation in females compared with males (p=0.050). Among the RCC patients with total nephrectomy, there was a significant LINC00365 up regulation in advanced stage compared with primary stage tumors (p=0.035). RCC patients older than 60 years old who were undergone the total nephrectomy had also significant LINC00365 up regulation compared with RCC patients younger than 60 years old (p=0.039)., Conclusions: given the significant increase in LINC00365 expression in advanced stage RCC tumors and patients over 60 years old who had total nephrectomy; it could serve as a useful diagnostic marker in screening programs for old high-risk individuals. It was also noticed that female RCC patients had elevated levels of LINC00365 expressions in their tumor samples, suggesting its potential use as a gender-specific diagnostic marker for high-risk females. Nevertheless, evaluating the levels of LINC00365 in serum samples of RCC patients is necessary to suggest that as a reliable diagnostic marker in clinical settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Increasing evidence highlights the important role of ubiquitination in cancer. The objective of our study is to establish a reliable marker for predicting clinical outcomes and treatment responses in patients with clear cell renal cell carcinoma (ccRCC) using genes related to ubiquitination (URGs). The URGs subtypes were identified using consensus clustering based on TCGA-KIRC, and a signature containing the prognostic differentially expressed genes of the subtypes was determined using LASSO and Cox regression analysis. To demonstrate the strength of the signature, verification analyses were performed on both E-MTAB-1980 and TCGA-KIRC test datasets. We developed a nomogram to enhance the effectiveness of our predictive tool. Risk genes expression was determined through RT-qPCR. Six genes were combined to create the URGs signature, which had a highly correlated with patient prognosis in patients with ccRCC. A nomogram was developed based on the URGs signature and clinicopathological characteristics. We found that the predictive power was substantially greater than the other individual predictors. Moreover, the study on the immune microenvironment revealed significant variations in the levels of immune cells and the expression of immune checkpoint genes among the groups categorized as high-risk and low-risk. Furthermore, it was found that immunotherapy yielded better outcomes in cohorts with low risk. The URGs signature might serve as a novel and powerful prognosis biomarker and offer a momentous reference for individualized treatment for patients in ccRCC., (© 2024. The Author(s).)

Aggressive clear cell renal cell carcinoma (ccRCC) has a bad prognosis. We seek new ccRCC biomarkers for diagnosis and treatment. We used exoRBase and The Cancer Genome Atlas Database to compare DEmRNAs, DEmiRNAs, DElncRNAs, and DEcircRNAs in ccRCC and normal renal tissues. CircRNAs and circRNAs targeting microRNAs (miRNAs) were anticipated and taken intersections, and several databases assessed the targeted link between common miRNAs and messenger RNAs (mRNAs). The Cancer Genome Atlas database was used to create a predictive mRNA signature that was validated in E-MTAB-1980. Finally, we examined competing endogenous RNA network miRNAs and long noncoding RNAs for ccRCC predictive biomarkers using overall survival analysis. We built the first competing endogenous RNA regulation network of circRNA-lncRNA-miRNA-mRNA and found that it substantially correlates with ccRCC prognosis. We unveiled ccRCC's posttranscriptional regulation mechanism in greater detail. Our findings identified novel biomarkers for ccRCC diagnosis, therapy, and prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

EVI2A has emerged as a significant biomarker in various diseases; however, its biological role and mechanism in kidney renal clear cell carcinoma (KIRC) remains unexplored. We used TCGA and GEO databases to analyze EVI2A gene expression comprehensively and performed pan-cancer assessments. Clinical relevance was evaluated through Kaplan-Meier analysis and ROC curves. The gene's immune relevance was explored through analyses of the tumor microenvironment (TME), Tumor Immune Single-cell Hub (TISCH), immune checkpoints, and immunotherapy sensitivity. Our results indicate that EVI2A expression is upregulated in KIRC, showing correlations with tumor grade and T/N/M stage. EVI2A demonstrates high diagnostic accuracy (AUC=0.906) and predicts poor overall and progression-free survival in KIRC patients. Furthermore, EVI2A expression exhibits significant associations with immunity, including TME scores and specific immune cell types such as Tfh cells, CD4 memory T cells, and CD8+ T cells. Elevated EVI2A expression suggests increased sensitivity to PD-1/CTLA-4 and tyrosine kinase inhibitors. In vitro assays confirmed the impact of EVI2A on KIRC behavior, with its knockdown resulting in reduced cell proliferation and migration. In conclusion, our comprehensive analysis identifies EVI2A as a promising biomarker and a novel therapeutic target for intervening in KIRC. These findings hold significant implications for further research and potential clinical applications., Competing Interests: The authors declare that there is no possible conflict of interest., (© 2024 The Authors.)

Recent studies indicate that CISD3 is crucial in mitochondrial function and tumorigenesis. Using various databases, we systematically analyzed its expression, prognostic value, and immune activity. Our findings show CISD3 is mainly expressed in tumor cells across cancers, with higher mRNA but lower protein levels, degraded post-translationally via the lysosomal pathway. In certain cancers, CISD3 expression is positively correlated with tumor-infiltrating immune cells. Prognostic analysis suggests dual roles as both protective and risk factors, notably an independent prognostic predictor in renal cell carcinoma (RCC). CISD3 copy number variations are linked to homologous recombination defects and tumor-specific neoantigens, negatively correlated with methylation levels. Pathway analysis reveals CISD3 involvement in oncogenic processes, such as proliferation inhibition and epithelial-mesenchymal transition. Protein interactions underline its role in mitochondrial metabolism and redox balance. Experiments confirm low CISD3 expression in cancers, with overexpression reducing proliferation, migration, invasion, and tumor growth in mice. Mechanistic studies indicate CISD3 overexpression disrupts mitochondrial function, increases ROS levels, decreases GSH/GSSG ratios and mitochondrial membrane potential, inhibiting antioxidant activity and promoting cell damage and ferroptosis, thus impeding cancer progression. This study highlights CISD3's potential as a prognostic biomarker and therapeutic target., (© 2024. The Author(s).)

Rho GTPase activating protein (ARHGAP) family genes play critical roles in the onset and progression of human cancer. Rho GTPase activating protein 9 (ARHGAP9) is upregulated in various tumors. However, far too little attention has been paid to the prognostic value of ARHGAP9 and correlation with immune infiltration in clear cell renal cell carcinoma (ccRCC). Our aim is to evaluate the prognostic significance of ARHGAP9 expression and its correlation with immune infiltration in ccRCC. Transcriptional expression profiles of ARHGAP9 between ccRCC tissues and normal tissues were downloaded from The Cancer Genome Atlas. The ARHGAP9 protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium. Receiver operating characteristic curve was used to differentiate ccRCC from adjacent normal tissues. The Kaplan-Meier method was conducted to assess the effect of ARHGAP9 on survival. Protein-protein interaction networks were constructed by the STRING. Functional enrichment analyses were performed using the "ClusterProfiler" package. The immune infiltration patterns were evaluated via the tumor immune estimation resource 2.0 and Tumor-Immune System Interaction Database. ARHGAP9 expression was substantially higher in ccRCC tissues than in adjacent normal tissues. Increased ARHGAP9 mRNA expression was shown to be linked to high TNM stage and lymph node metastases. The diagnostic value of ARHGAP9 gene expression data was assessed using receiver operating characteristic curve analysis. The survival analysis module of GEPIA2 and the Kaplan-Meier plotter both showed ccRCC patients with high-ARHGAP9 had a worse prognosis than those with low-ARHGAP9. Correlation analysis indicated ARHGAP9 mRNA expression was significantly correlated with tumor purity and immune infiltrates. These findings demonstrate that upregulated ARHGAP9 indicates poor prognosis and immune infiltration in ccRCC. The current findings suggest that ARHGAP9 can be an effective biomarker and potential therapeutic strategy for ccRCC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aromatic caninurine formamase (AFMID) is an enzyme involved in the tryptophan pathway, metabolizing N-formylkynurenine to kynurenine. AFMID had been found significantly downregulated in clear cell renal cell carcinoma (ccRCC) in both tissue and urine samples. Although ccRCC is characterized by a typical Warburg-like phenotype, mitochondrial dysfunction, and elevated fat deposition, it is unknown whether AFMID plays a role in tumorigenesis and the development of ccRCC. In the present study, AFMID overexpression had inhibitory effects for ccRCC cells, decreasing the rate of cell proliferation. Quantitative proteomics showed that AFMID overexpression altered cellular signaling pathways involved in cell growth and cellular metabolism pathways, including lipid metabolism and inositol phosphate metabolism. Further urine proteomic analysis indicated that cellular function dysfunction with AFMID overexpression could be reflected in the urine. The activity of predicted upregulators DDX58, TREX1, TGFB1, SMARCA4, and TNF in ccRCC cells and urine showed opposing change trends. Potential urinary biomarkers were tentatively discovered and further validated using an independent cohort. The protein panel of APOC3, UMOD, and CILP achieved an AUC value of 0.862 for the training cohort and 0.883 for the validation cohort. The present study is of significance in terms of highlighting various aspects of pathway changes associated with AFMID enzymes, discovering potential specific biomarkers for potential patient diagnosis, and therapeutic targeting.

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., (© 2024. The Author(s).)

Background: Integrated immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) are now the recommended first-line therapy to manage renal cell carcinoma (mRCC). Proteasome 26S subunit non-ATPase 2 (PSMD2) overexpression in tumors has been correlated with tumor progression. Currently, mRCC lacks an established biomarker for the combination of ICI+TKI., Methods: This study involved RNA sequencing of RCC patients from two cohorts treated with ICI+TKI (ZS-MRCC and JAVELIN-Renal-101). We utilized immunohistochemistry alongside flow cytometry, aiming at assessing immune cell infiltration and functionality in high-risk localized RCC samples. Response and progression-free survival (PFS) were evaluated relying upon RECIST criteria., Results: PSMD2 was significantly overexpressed in advanced RCC and among non-responders to ICI+TKI therapy. Overexpressed PSMD2 was correlated with poor PFS in the ZS-MRCC and JAVELIN-101 cohorts. Multivariate Cox analysis validated PSMD2 as an independent PFS predictor. PSMD2 overexpression was related to a reduction in CD8 + T cells, especially GZMB + CD8 + T cells, besides an increase in PD1 + CD4 + T cells. Additionally, tumors with high PSMD2 levels showed enhanced T cell exhaustion levels and a higher regulatory T cell presence. A Machine Learning (ML) model based on PSMD2 expression and other screened factors was subsequently developed to predict the effectiveness of ICI+TKI., Conclusions: Elevated PSMD2 expression is linked to resistance and decreased PFS in mRCC patients undergoing ICI+TKI therapy. High PSMD2 levels are also associated with impaired function and increased exhaustion of tumor-infiltrating lymphocytes. An ML model incorporating PSMD2 expression could potentially identify patients who may have a higher likelihood of benefiting from ICI+TKI., (© 2024. Springer Nature Switzerland AG.)

This study aimed to investigate the role of cluster of differentiation 276 (CD276) in evaluating the prognosis of clear cell renal carcinoma (ccRCC) and to build a nomogram for predicting ccRCC progression post-surgery. Using data downloaded from The Cancer Genome Atlas (TCGA) database, we constructed a Kaplan-Meier (KM) curve depicting the relationship between CD276 expression levels and the progression-free interval (PFI) in 539 ccRCC cases. We further validated this by plotting a KM curve of the relationship between CD276 expression levels and PFI in 116 ccRCC patients from our hospital. Using clinical data collected from 116 patients, we identified independent risk factors affecting postoperative PFI in patients with ccRCC through univariate and multivariate COX analyses and created a nomogram for visual representation. Both TCGA and clinical data revealed a negative correlation between the expression levels of CD276 and PFI (p < 0.05). Univariate COX analysis revealed that the prognostic nutritional index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory index, World Health Organization grading, tumor diameter, CD276 expression levels, T stage, and N stage were related to PFI (p < 0.05). Furthermore, multivariate COX analysis indicated that tumor diameter and CD276 expression levels were independent risk factors for postoperative PFI in patients with ccRCC (p < 0.05). The calibration curve of the established nomogram exhibited a slope close to 1, with a Hosmer-Lemeshow goodness-of-fit test result of 2.335 and a p-value of 0.311. In patients with ccRCC, a negative correlation was noted between tumor CD276 expression and PFI. The larger the tumor diameter and the higher the tumor CD276 expression level, the shorter is the PFI., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background: The identification of reliable prognostic markers is crucial for optimizing patient management and improving clinical outcomes in clear cell renal cell carcinoma (ccRCC)., Methods: We used the GSE89563 dataset from the GEO database and the Kidney Clear Cell Carcinoma (KIRC) dataset from the TCGA database to develop a prognostic model based on weighted gene co-expression network analysis (WGCNA) and non-negative matrix factorization (NMF) to predict disease progression and prognosis in ccRCC., Result: We utilized WGCNA to identify risk genes and applied NMF to stratify high-risk populations in ccRCC. We characterized the immune gene features of these high-risk groups and ultimately developed a risk prediction model for ccRCC patients using a Lasso regression approach. The risk score was calculated as follows: Risk score = SUM (-0.136394797 ANK3 + 0.004238138 BIVM&#95;ERCC5 - 0.046248451 C4orf19 - 0.036013206 F2RL3 - 0.125531316 GNG7 - 0.012698109 METTL7A + 0.078462369 MSTO1 - 0.050450656 PINK1 - 0.059446590 SLC16A12 - 0.039883686 SLC2A9 + 0.083310722 TLCD1 - 0.059801739 WDR72 + 0.071430088 ZNF117)., Conclusion: We develop a prognostic model for clear cell renal cell carcinoma and analyzed immune response in subgroups and confirmed protein-level expression concordance., Competing Interests: Disclosure Not applicable., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosure The authors report no financial or any other conflicts of interest in this work.

Context.—: Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors., Objective.—: To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better., Design.—: The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases., Results.—: The mean age of patients was 49.6 years, and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance, whereas the others appeared purely solid. Microscopically, all 18 tumors shared a similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression., Conclusions.—: Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Xp11.2 translocation renal cell carcinomas (tRCC) are a rare and highly malignant type of renal cancer, lacking efficient diagnostic indicators and therapeutic targets. Through the analysis of public databases and our cohort, we identified NMRK2 as a potential diagnostic marker for distinguishing Xp11.2 tRCC from kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) due to its specific upregulation in Xp11.2 tRCC tissues. Mechanistically, we discovered that TFE3 fusion protein binds to the promoter of the NMRK2 gene, leading to its upregulation. Importantly, we established RNA- and protein-based diagnostic methods for identifying Xp11.2 tRCC based on NMRK2 expression levels, and the diagnostic performance of our methods was comparable to a dual-color break-apart fluorescence in situ hybridization assay. Moreover, we successfully identified fresh Xp11.2 tRCC tissues after surgical excision using our diagnostic methods and established an immortalized Xp11.2 tRCC cell line for further research purposes. Functional studies revealed that NMRK2 promotes the progression of Xp11.2 tRCC by upregulating the NAD + /NADH ratio, and supplementation with β-nicotinamide mononucleotide (NMN) or nicotinamide riboside chloride (NR), effectively rescued the phenotypes induced by the knockdown of NMRK2 in Xp11.2 tRCC. Taken together, these data introduce a new diagnostic indicator capable of accurately distinguishing Xp11.2 tRCC and highlight the possibility of developing novel targeted therapeutics. © 2024 The Pathological Society of Great Britain and Ireland., (© 2024 The Pathological Society of Great Britain and Ireland.)

Renal cell carcinoma with clear cells (ccRCC) is the most frequent kind; it accounts for almost 70% of all kidney cancers. A primary objective of current research was to find genes that may be used in ccRCC gene therapy to understand better the molecular pathways underlying the disease. Based on PubMed microarray searches and meta-analyses, we compared overall survival and recurrence-free survival rates in ccRCC patients with those in healthy samples. The technique was followed by a KEGG pathway and Gene Ontology (GO) function analyses, both performed in conjunction with the approach. Tumor immune estimate and multi-gene biomarkers validation for clinical outcomes were performed at the molecular and clinical cohort levels. Our analysis included fourteen GEO datasets based on inclusion and exclusion criteria. A meta-analysis procedure, network construction using PPIs, and four significant gene identification standard algorithms indicated that 11 genes had the most important differences. Ten genes were upregulated, and one was downregulated in the study. In order to analyze RFS and OS survival rates, 11 genes expressed in the GEPIA2 database were examined. Nearly nine of eleven significant genes have been found to beinvolved in tumor immunity. Furthermore, it was found that mRNA expression levels of these genes were significantly correlated with experimental literature studies on ccRCCs, which explained these findings. This study identified eleven gene panels associated with ccRCC growth and metastasis, as well as their immune system infiltration., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC., Purpose: This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets., Methods: The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan-Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients., Results: A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients., Conclusions: Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Objectives: Renal cell carcinoma (RCC) is the most common cancer of the kidney. This study aims to evaluate the potential predictive value of E-cadherin, a marker of the epithelial mesenchymal transit (EMT) process that has been associated with tumor metastasis., Methods: We searched PubMed, Embase, and Cochrane Library to identify prospective studies. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were summarized to validate the relationship between E-cadherin and survival and clinical characteristics. The quality of the included studies was assessed using the NOS table. Then, we analyzed genetic data and clinical characteristics from The Cancer Genome Atlas Program (TCGA) database using R language with the dplyr package for validation., Results: Including 21 articles. The analysis revealed a strong link between high E-cadherin expression and favorable prognosis (for OS, HR = 0.35, 95% CI: 0.19-0.62; for PFS, HR = 0.19, 95% CI: 0.03-0.53; for DSS, HR = 0.25, 95% CI: 0.08-0.76; for RFS, HR = 0.71, 95% CI: 0.44-1.16; for DFS, HR = 0.28, 95% CI: 0.13-0.61; for T stage, OR = 0.21, 95% CI: 0.11-0.41; for N stage, OR = 0.07, 95%CI: 0.02-0.25; for M stage, OR = 0.12, 95% CI: 0.02-0.60; for clinical stage, OR = 0.29, 95% CI: 0.18-0.47; for nuclear grade, OR = 0.23, 95% CI: 0.13-0.41; for tumor size, OR = 0.49, 95% CI: 0.26-0.92). The findings were supported by bioinformatic analysis which used TCGA RCC patient's cohort ( P < 0.01)., Conclusion: Based on the current data, E-cadherin may predict a better prognosis in RCC patients.

Historically, papillary renal cell carcinoma (PRCC) was divided into two types, type 1 and type 2, based solely on morphology. However, it is apparent that PRCC is far more complex and represents a histological, clinical, and molecular spectrum. There has been a significant evolution in our understanding of PRCC, highlighted by the recognition of new and molecularly defined entities that were previously included in PRCC type 2. This contemporary review addresses the evolving concepts regarding the PRCC, including why it is no longer needed to subtype PRCC, the current molecular landscape, prognostic parameters, and PRCC variants, including biphasic PRCC, papillary renal neoplasm with reverse polarity, and Warthin-like PRCC. Pathologists should also be aware of the potential mimickers of both low-grade and high-grade PRCCs as well as some new and emerging entities that may show papillary growth that should be excluded in the diagnostic workup. The evolving knowledge of PRCC biomarkers, morphologic patterns, and PRCC variants could also have important implications for clinical management. Lastly, the heterogeneity within the PRCC spectrum needs to be further studied, aiming to better stratify PRCC for appropriate clinical management and systemic therapy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Clear renal cell carcinoma (ccRCC) is a common and deadly urinary system tumor. The TNM system determines treatment and prognosis based on cancer advancement. While nephron-sparing surgery is an option for localized ccRCC, advanced cases are challenging, and molecular-targeted therapy is crucial., Methods: Here, we implemented microarray datasets to identify a total of 119 differentially expressed genes (DEGs) and ten hub genes by a protein-protein interaction network (PPI) and performed module analysis through STRING and Cytoscape., Results: Data from this analysis shed light on a positive correlation between SLC12A3 (solute carrier family 12 member 3) and tumor-correlated cells. SLC12A3 can predict prognosis and immune infiltration levels in KIRC patients., Conclusion: Our findings demonstrated that SLC12A3 expression accounts for favorable prognosis and increased immune infiltration of various cell types. This could lead to potential therapeutic aims and biomarkers for KIRC (kidney renal clear cell carcinoma).

Natural products are chemical compounds produced by living organisms. They are isolated and purified to determine their function and can potentially be used as therapeutic agents. The ability of some bioactive natural products to modify the course of cancer is fascinating and promising. In the past 50 years, there have been advancements in cancer therapy that have increased survival rates for localized tumors. However, there has been little progress in treating advanced renal cell carcinoma (RCC), which is resistant to radiation and chemotherapy. Oncogenes and tumor suppressors are two roles played by microRNAs (miRNAs). They are involved in important pathogenetic mechanisms like hypoxia and epithelial-mesenchymal transition (EMT); they control apoptosis, cell growth, migration, invasion, angiogenesis, and proliferation through target proteins involved in various signaling pathways. Depending on their expression pattern, miRNAs may identify certain subtypes of RCC or distinguish tumor tissue from healthy renal tissue. As diagnostic biomarkers of RCC, circulating miRNAs show promise. There is a correlation between the expression patterns of several miRNAs and the prognosis and diagnosis of patients with RCC. Potentially high-risk primary tumors may be identified by comparing original tumor tissue with metastases. Variations in miRNA expression between treatment-sensitive and therapy-resistant patients' tissues and serum allow for the estimation of responsiveness to target therapy. Our knowledge of miRNAs' function in RCC etiology has a tremendous uptick. Finding and validating their gene targets could have an immediate effect on creating anticancer treatments based on miRNAs. Several miRNAs have the potential to be used as biomarkers for diagnosis and prognosis. This review provides an in-depth analysis of the current knowledge regarding natural compounds and their modes of action in combating cancer. Also, this study aims to give information about the diagnostic and prognostic value of miRNAs as cancer biomarkers and their involvement in the pathogenesis of RCC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Renal cell carcinoma is the most common adult renal solid tumor and the deadliest urological cancer, with clear cell renal cell carcinoma (ccRCC) being the predominant subtype. The PI3K/AKT signaling pathway assumes a central role in ccRCC tumorigenesis, wherein its abnormal activation confers a highly aggressive phenotype, leading to swift resistance against current therapies and distant metastasis. Thus, treatment resistance and disease progression remain a persistent clinical challenge in managing ccRCC effectively. PTEN, an antagonist of the PI3K/AKT signaling axis, emerges as a crucial factor in tumor progression, often experiencing loss or inactivation in ccRCC, thereby contributing to elevated mortality rates in patients. Therefore, understanding the molecular mechanisms underlying PTEN suppression in ccRCC tumors holds promise for the discovery of biomarkers and therapeutic targets, ultimately enhancing patient monitoring and treatment outcomes. The present review aims to summarize these mechanisms, emphasizing their potential prognostic, predictive, and therapeutic value in managing ccRCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Fumarate hydratase (FH)-deficient renal cell carcinomas are rare neoplasms characterized by wide morphologic heterogeneity and pathogenetic mutations in the FH gene. They often show aggressive behavior with rapid diffusion to distant organs, so novel therapeutic scenarios have been explored, including EGFR inhibitors and PD-L1 expression for targeted immunotherapy. Herein, we investigated a series of 11 primary FH-deficient renal cell carcinomas and 7 distant metastases to evaluate tumor heterogeneity even in metastatic sites and estimate the specific spread rates to various organs. Furthermore, the tumors were tested for immunohistochemical PD-L1 expression and EGFR mutations. Most metastatic cases involved the abdominal lymph nodes (4/7; 57%), followed by the peritoneum (3/7; 42%), the liver (2/7; 29%), and the lungs (1/7; 14%). Six metastatic localizations were histologically documented, revealing a morphologic heterogeneous architecture often differing from that of the corresponding primary renal tumor. Peritoneal involvement morphologically resembled a benign reactive mesothelial process or primary peritoneal mesothelioma, thus advocating to perform an accurate immunohistochemical panel, including PAX8 and FH, to reach a proper diagnosis. A pure low-grade succinate dehydrogenase-looking primary FH-deficient renal cell carcinoma was also recorded. As for therapy, significant PD-L1 labeling was found in 60% of primary renal tumors, whereas none of them carried pathogenetic EGFR mutations. Our data show that FH-deficient renal cell carcinoma may be morphologically heterogeneous in metastases as well, which involve the lymph nodes, the liver, and the peritoneum more frequently than other renal tumors. Due to the high frequency of this latter (42%), pathologists should always be concerned about ruling out mesothelial-derived mimickers, and the occurrence of rarer, primary, low-grade-looking types. Finally, contrary to EGFR mutations, PD-L1 expression could be a possible predictive biomarker for the therapy of these tumors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Numerous studies have shown that the Krüppel-like factors (KLFs) family of transcription factors regulate various eukaryotic physiological processes including the proliferation, differentiation, senescence, death, and carcinogenesis of animal cells. In addition, they are involved in the regulation of key biological processes such as cell cycle, DNA repair, and immune response. Current studies focus on investigating the role of KLFs in normal physiological conditions and the incidence and development of diseases. However002C the significance of KLFs family genes in clear cell renal cell carcinoma (ccRCC) remains partly understood; therefore, an in-depth investigation of their role and clinical value in this cancer is desired. The study aimed to investigate the role of KLF family genes in the incidence, development, and prognosis of ccRCC, and to identify the related potential biomarkers and therapeutic targets. The expression of KLFs in the RNA sequencing data of 613 ccRCCs from the TCGA database was analyzed using R software, and UALCAN and GEPIA assessed the expression of KLF genes in ccRCC. Real-time fluorescence quantitative PCR analysis was performed using 10 pairs of paired ccRCC sample tissues and renal cancer cell lines from the First Affiliated Hospital of Nanchang University. Overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of Kidney Clear Cell Carcinoma (KIRC) samples at differential expressions of KLFs in the TCGA database were analyzed using the R software, followed by generating a nomogram prediction model. GSCALite assessed the interactions of KLF genes with miRNAs and generated network maps. Protein interaction network maps of 50 neighboring genes associated with KLF mutations were analyzed using STRING with GO and KEGG functional enrichment analyses. The cBioPortal determined the probability of KLF gene mutations and their impact on OS and disease-free survival (DFS) in patients with ccRCC. Immune cell infiltration of KLFs was analyzed using TIMER. Finally, GSCALite was used to analyze the drug sensitivity and associated pathways of action of KLFs. Correlation validation using cellular experiments. KLF3/5/9/15 were significantly downregulated in ccRCC tissues, whereas KLF16/17 were upregulated compared with the adjacent tissues. Patients with high mRNA levels of KLF16/17 showed significantly lower OS, PFI, and DSS, whereas KLF3/5/9 showed a reverse trend. In patients with ccRCC, a significant correlation was observed between KLF mutations and OS and DSS. Furthermore, the correlation of KLF3/5/9 with immune cell infiltration was stronger than that of KLF15/16, while KLF17 was significantly associated with the Epithelial-Mesenchymal Transition (EMT) pathway. Overexpression of KLF5 inhibits the proliferative and migratory capacity of renal cancer cells (786-O and OS-RC-2), as well as their sensitivity to relevant small molecule drugs. Our research revealed the expression levels and biological significance of KLF genes in ccRCC, particularly highlighting the potential of KLF5 as a promising biomarker and therapeutic target for effective prognosis and diagnosis of ccRCC., (© 2024. The Author(s).)

SHC1 plays a crucial regulatory role in various tumors, but its significance in predicting prognosis and immune response in clear cell renal cell carcinoma (ccRCC) is yet to be determined. In this study, we conducted a bioinformatics analysis of SHC1 expression, prognosis, and immunological functions in ccRCC using multiple databases. The association between SHC1 and immune infiltration, immune escape, and immunotherapy in ccRCC was systematically established. In addition, we validated our results by western blot of tumor and adjacent-tumor samples from nine ccRCC patients, as well as three renal carcinoma cell lines compared to a normal renal cell line. Our analysis revealed that the mRNA expression level of SHC1 in ccRCC tissues is significantly higher than that in normal tissues. Consistently, western blot experiment showed ccRCC tissues and cell lines exhibit higher protein levels that normal tissues and cell lines. Importantly, patients with low expression of SHC1 demonstrated a higher survival rate, indicating that SHC1 could serve as an independent prognostic factor for predicting survival in ccRCC. Additionally, high expression of SHC1 was associated with increased severe immune cell infiltration, enhanced immune escape, and higher immunotherapy scores. Hence, SHC1 emerges as a novel and easily detectable biomarker for predicting clinical outcomes, immune escape, and immunotherapy response in patients with ccRCC., (© 2024. The Author(s).)

Background: Protein information is often replaced by RNA data in studies to understand cancer-related biological processes or molecular functions, and proteins of prognostic significance in Kidney clear cell carcinoma (KIRC) remain to be mined. Methods: The cancer genome atlas program (TCGA) data was utilized to screen for proteins that are prognostically significant in KIRC. Machine learning algorithms were employed to develop protein prognostic models. Additionally, immune infiltration abundance, somatic mutation differences, and immunotherapeutic responses were analyzed in various protein risk subgroups. Ultimately, the validation of protein-coding genes was confirmed by utilizing an online database and implementing quantitative real-time PCR (qRT-PCR). Results: The patients were divided into two risk categories based on prognostic proteins, and notable disparities in both overall survival (OS) and progression free interval (PFI) were observed between the two groups. The OS was more unfavorable in the high-risk group, and there was a noteworthy disparity in the level of immune infiltration observed between the two groups. In addition, the nomogram showed high accuracy in predicting survival in KIRC patients. Conclusion: In this research, we elucidated the core proteins associated with prognosis in terms of survival prediction, immunotherapeutic response, somatic mutation, and immune microenvironment. Additionally, we have developed a reliable prognostic model with excellent predictive capabilities., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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., (© 2024. The Author(s).)

Background: Zinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated., Methods: In this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients., Results: The pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects., Conclusions: ZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC., (© 2024. The Author(s).)

Introduction Background: Disulfidptosis is a prevalent apoptotic mechanism, intrinsically linked to cancer prognosis. However, the specific involvement of disulfidptosis-related long non-coding RNA (DRLncRNAs) in Kidney renal clear cell carcinoma (KIRC) remains incompletely understood. This study aims to elucidate the potential prognostic significance of disulfidptosis-related LncRNAs in KIRC., Materials and Methods: Expression profiles and clinical data of KIRC patients were retrieved from the TCGA database to discern differentially expressed DRLncRNAs correlated with overall survival. Cox univariate analysis, Lasso Regression, and Cox multivariate analysis were used to construct a clinical prediction model., Results: Six signatures, namely FAM83C.AS1, AC136475.2, AC121338.2, AC026401.3, AC254562.3, and AC000050.2, were established to evaluate overall survival (OS) in the context of Kidney renal clear cell carcinoma (KIRC) in this study. Survival analysis and ROC curves demonstrated the strong predictive performance of the associated signature. The nomogram exhibited accurate prognostic predictions for overall patient survival, offering substantial clinical utility. Gene set enrichment analysis revealed that risk signals were enriched in various immune-related pathways. Furthermore, the risk features exhibited significant correlations with immune cells, immune function, immune cell infiltration, and immune checkpoints., Conclusion: This study has unveiled, for the first time, six disulfdptosis-related LncRNA signatures, laying a solid foundation for enhanced and precise prognostic predictions in KIRC., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Renal cell carcinoma (RCC) is a common malignant tumor with a high incidence in males and the elderly, and clear cell RCC (ccRCC) is the most common RCC subtype. ccRCC is highly metastatic with a poor prognosis. Therefore, it is crucial to obtain a detailed understanding of the molecular mechanism of ccRCC and to identify suitable biomarkers to realize early diagnosis and improve prognosis., Methods: We analyzed data from the Cancer Genome Atlas, investigated the overall differential expression of CD276 in ccRCC, and evaluated the influence of CD276 on patient survival and prognosis. We also performed gene set enrichment analysis (GSEA) and pathway enrichment analysis and investigated cell infiltration and drug responsiveness to further assess the regulatory effect of CD276 on ccRCC. Furthermore, we verified CD276 expression in RCC cell lines and control cell lines., Results: The CD276 expression level in ccRCC samples was higher than that in corresponding samples adjacent to the tumors. Moreover, high CD276 expression levels were positively correlated with poor prognosis in patients with RCC. GSEA revealed that CD276 was significantly involved in immune-related pathways, and the level of CD276 expression was confirmed as associated with immune cell infiltration to some extent. Notably, some drugs were predicted to act on CD276, and this was confirmed by molecular docking. Furthermore, high levels of CD276 expression in RCC cell lines were verified., Conclusion: CD276 expression was significantly increased in ccRCC tissues and cells and positively correlated with patient prognosis. CD276 is a potential prognostic biomarker of ccRCC. Overall, this study provides a potential therapeutic strategy for ccRCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development and progression of many cancers. Partial EMT (pEMT) could represent a critical step in tumor migration and dissemination. Sarcomatoid renal cell carcinoma (sRCC) is an aggressive form of renal cell carcinoma (RCC) composed of a carcinomatous (sRCC-Ca) and sarcomatous (sRCC-Sa) component. The role of (p)EMT in the progression of RCC to sRCC remains unclear. The aim of this study was to investigate the involvement of (p)EMT in RCC and sRCC. Tissue samples from 10 patients with clear cell RCC (ccRCC) and 10 patients with sRCC were selected. The expression of main EMT markers (miR-200 family, miR-205, SNAI1/2, TWIST1/2, ZEB1/2, CDH1/2, VIM) was analyzed by qPCR in ccRCC, sRCC-Ca, and sRCC-Sa and compared to non-neoplastic tissue and between both groups. Expression of E-cadherin, N-cadherin, vimentin and ZEB2 was analyzed using immunohistochemistry. miR-200c was downregulated in sRCC-Ca compared to ccRCC, while miR-200a was downregulated in sRCC-Sa compared to ccRCC. CDH1 was downregulated in sRCC-Sa when compared to any other group. ZEB2 was downregulated in ccRCC and sRCC compared to corresponding non-neoplastic kidney. A positive correlation was observed between CDH1 expression and miR-200a/b/c. Our results suggest that full EMT is not present in sRCC. Instead, discreet molecular differences exist between ccRCC, sRCC-Ca, and sRCC-Sa, possibly representing distinct intermediary states undergoing pEMT., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A macroscopic perspective is indispensable for understanding the intricate relationship between deubiquitinases and tumorigenesis. Proteomics has been proposed as a viable approach for elucidating the complex role of deubiquitylation in cellular progression. Instead of studying the function of a single ubiquitinase, research on a deubiquitinase family with similar catalytic core(s) may provide a new perspective for the pathological understanding of cancer. The Ubiquitin C-terminal hydrolase L (UCHL) family consists of four members: UCHL1, UCHL3, UCHL5, and BRAC1 associated protein-1 (BAP1), and they have been implicated in tumorigenesis and metastasis. Some members are considered hallmarks of intracranial lesions, colon cancer, chromatin remodeling, and histone stability. The present study uncovered an unknown correlation between the UCHL family and renal cancer. We discovered that UCHLs exhibit diverse regulatory effects in renal cancer, establishing connections between the renal cancer and truncated gene mutations, mitochondrial energetic metastasis, immune cell infiltration, and chromosomal stability of UCHLs family. Notably, we found that the increase of UCHL5 expression in renal cancer cells decreases the antigen processing and presentation of RCC tumor-infiltrating B cells. Further research identified that the expression of UCHL5 in RCC tumors is correlated with transport proteins, which led us to find that the abundance of UCHL5 in the blood of late-stage renal cell cancer patients is upregulated from 18 ng/L to 500 ng/L. Therefore, we propose that the abundance of UCHL5 in patients' blood can be a possible indicator of poor prognosis for renal cell cancer., (© 2024. The Author(s).)

Introduction: Renal cell carcinoma is one of the ten more common malignant tumors worldwide, with a high incidence and mortality rate. Kidney cancer frequently presents at an advanced stage, and it is almost invariably fatal. Much progress has been made in identifying molecular targets for therapy in the hope of improving survival rates, but still, we have no good markers for early detection or progression of the disease. Von Hippel Lindau syndrome (VHL) is an autosomal dominant cancer hereditary syndrome in which affected individuals are at risk of developing bilateral and multifocal renal cell carcinomas (RCC) as well as other tumors. These patients provide an ideal platform to investigate the potential of urinary exosomal miRNA biomarkers in the early development of ccRCC, as these patients are regularly imaged and tumors are actively monitored until the tumor reaches 3 cm before surgical excision. This allows for pre- and post-surgical urine collection and comparison to excised tumor tissues. Studying different biomarkers in urine can provide comprehensive molecular profiling available to patients and physicians and can be a great source of additional tumor genetic information., Methods: Pre- and postoperative urine samples were obtained from a cohort of VHL patients undergoing surveillance and surgical excision of ccRCCs, and exosomes were extracted. MicroRNA-Seq analysis was performed on miRNA extracted from both urine-derived exosomes and FFPE material from excised ccRCCs., Results: MicroRNA-Seq analysis highlighted a significant difference in the urinary exosome-derived miRNA expression profiles between VHL patients and normal control individuals. This included decreased expression of the miR-320 family, such as miR-320a, known to be decreased in sporadic ccRCC and suppressed by the HIF1α transcription factor activated by the loss of the VHL gene. MiR-542-5p represented a potential marker of VHL-associated ccRCC that was lowly expressed in normal control urinary exosomes, significantly increased in the preoperative urinary exosomes of tumor-bearing VHL patients, and subsequently reduced to normal levels of expression after tumor excision. In concordance with this, the expression of miR-542-5p was increased in the VHL-associated ccRCC in comparison to the normal kidney., Conclusions: This study shows the potential for miRNA profiling of exosomes from readily available biofluids to both distinguish VHL patient urine from normal control urine microRNAs and to provide biomarkers for the presence of VHL syndrome-associated ccRCC. Further validation studies are necessary to demonstrate the utility of urinary exosome-derived miRNAs as biomarkers in kidney cancer.

Recently, mounting evidence has highlighted the essential function of the C-terminal binding protein-1 divergent transcript (CTBP1-DT) in malignancies. However, its role in kidney renal clear cell carcinoma (KIRC) remains largely unknown. Our study aimed to identify the potential function of CTBP1-DT in KIRC. RT-qPCR, Kaplan-Meier survival analysis, Cox regression analysis, and nomogram analysis were utilized to determine the expression and effects of CTBP1-DT on survival. The subcellular localization of CTBP1-DT was determined using RNA fluorescence in situ hybridization (FISH). To investigate the functions of CTBP1-DT in regulating KIRC cell proliferation, migration, invasion, lipid synthesis, and apoptosis, we conducted CCK8, EdU, Transwell, and Oil Red O staining and cell apoptosis staining assays. The relationships between CTBP1-DT and the tumor microenvironment were investigated with multiple bioinformatics analysis algorithms and databases, including CYBERSORT, TIMER2, Spearman correlation test, tumor mutation burden (TMB), microsatellite instability (MSI), and immunophenoscore (IPS). According to our results, CTBP1-DT is a lncRNA located in the nucleus that is significantly upregulated in KIRC and is correlated with better clinical outcomes. Downregulating CTBP1-DT inhibited cell viability, migration, invasion, and lipid synthesis but triggered cell apoptosis. Additionally, we explored the potential effect of CTBP1-DT in regulating immune cell infiltration in KIRC and other malignancies. Furthermore, CTBP1-DT could be used to predict the effectiveness of targeted drugs and immune checkpoint inhibitors. In conclusion, we identified CTBP1-DT as a potential immunological biomarker and discovered the potential role of CTBP1-DT in regulating lipid synthesis and apoptosis resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/aim: The management of patients with clear cell renal cell carcinoma (ccRCC) includes prognosis assessment based on TNM classification and biochemical markers. This approach stratifies patients with advanced ccRCC into groups of favorable, intermediate, and poor prognosis. The aim of the study was to improve prognosis estimation using microRNAs involved in the pathogenesis of ccRCC., Patients and Methods: The study was based on a histologically-verified set of matched ccRCC FFPE tissue samples (normal renal tissue, primary tumor, metastasis, n=20+20+20). The expression of 2,549 microRNAs was analyzed using the SurePrint G3 Human miRNA microarray kit (Agilent Technologies). Prognostic value of significantly deregulated microRNAs was further evaluated on microRNA expression and clinical data of 475 patients obtained from TCGA Kidney Clear Cell Carcinoma (KIRC) database., Results: There were 13 up-regulated and 6 down-regulated microRNAs in tumor tissues compared to control tissues. Among them, survival analysis revealed those with prognostic significance. Patients with high expression of miR-21, miR-27a, miR-34a, miR-106b, miR-210, and miR-342 showed significantly unfavorable outcome. The opposite was observed for miR-30e, patients with low expression had significantly shorter survival., Conclusion: The inclusion of these microRNAs in a prognostic panel holds the potential to enhance stratification scoring systems, on which the treatment of ccRCC patients is based., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Clear cell renal cell carcinoma (ccRCC) is the most common form of RCC. It is characterized by resistance to traditional radiotherapy and chemotherapy, as well as an unfavorable clinical prognosis. Although TYMP is implicated in the advancement of tumor progression, the role of TYMP in ccRCC is still not understood. Heightened TYMP expression was identified in ccRCC through database mining and confirmed in RCC cell lines. Indeed, TYMP knockdown impacted RCC cell proliferation, migration, and invasion in vitro. TYMP showed a positive correlation with clinicopathological parameters (histological grade, pathological stage). Moreover, patients with high TYMP expression were indicative of poor prognosis in TCGA-ccRCC and external cohorts. The results of single-cell analysis showed that the distribution of TYMP was predominantly observed in monocytes and macrophages. Furthermore, there is a significant association between TYMP and immune status. Methylation analysis further elucidated the relationship between TYMP expression and multiple methylation sites. Drug sensitivity analysis unveiled potential pharmaceutical options. Additionally, mutation analyses identified an association between TYMP and the ccRCC driver genes like BAP1 and ROS1. In summary, TYMP may serve as a reliable prognostic indicator for ccRCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Renal cell carcinoma (RCC) is one of the most common malignant tumors of the kidney, presenting significant challenges for clinical diagnosis and treatment. Macrophages play crucial roles in RCC, promoting tumor progression and warranting further investigation. Previous studies have identified LHFPL2 as a transmembrane protein associated with reproduction, but its relationship with tumors or macrophages has not been discussed. This study utilized transcriptomic sequencing data from 609 KIRC patients in the TCGA database and single-cell sequencing data from 34,326 renal carcinoma cells for subsequent analysis. We comprehensively evaluated the expression of LHFPL2 and its relationship with clinical features, tumor prognosis, immune infiltration, and mutations. Additionally, we further assessed the correlation between LHFPL2 and macrophage M2 polarization using single-cell data and explored its potential as a cancer therapeutic target through molecular docking. The results demonstrated that LHFPL2 is upregulated in RCC and associated with poor survival rates. In clinical staging, the proportion of malignant and high-metastasis patients was higher in the high- LHFPL2 group than in the low- LHFPL2 group. Furthermore, we found that LHFPL2 influences RCC immune infiltration, with its expression positively correlated with various immune checkpoint and M2-related gene expressions, positively associated with M2 macrophage infiltration, and negatively correlated with activated NK cells. Moreover, LHFPL2 showed specific expression in macrophages, with the high-expression subgroup exhibiting higher M2 polarization, hypoxia, immune evasion, and angiogenesis scores, promoting tumor progression. Finally, we predicted several potential drugs targeting LHFPL2 , such as conivaptan and nilotinib. Our analysis elaborately delineates the immune characteristics of LHFPL2 in the tumor microenvironment and its positive correlation with macrophage M2 polarization, providing new insights into tumor immunotherapy. We also propose potential FDA-approved drugs targeting this gene, which should be tested for their binding effects with LHFPL2 in future studies.

Renal cell carcinoma (RCC), accounting for 90% of all kidney cancer, is categorized into clear cell RCC (ccRCC) and non-clear cell RCC (non-ccRCC) for treatment based on the current NCCN Guidelines. Thus, the classification will be associated with therapeutic implications. This study aims to identify novel biomarkers to differentiate ccRCC from non-ccRCC using bioinformatics and machine learning. The gene expression profiles of ccRCC and non-ccRCC subtypes (including papillary RCC (pRCC) and chromophobe RCC (chRCC)), were obtained from TCGA. Differential expression genes (DEGs) were identified, and specific DEGs for ccRCC and non-ccRCC were explored using a Venn diagram. Gene Ontology and pathway enrichment analysis were performed using DAVID. The top ten expressed genes in ccRCC were then selected for machine learning analysis. Feature selection was operated to identify a minimum highly effective gene set for constructing a predictive model. The expression of best-performing gene set was validated on tissue samples from RCC patients using immunohistochemistry techniques. Subsequently, machine learning models for diagnosing RCC were developed using H-scores. There were 910, 415, and 835 genes significantly specific for DEGs in ccRCC, pRCC, and chRCC, respectively. Specific DEGs in ccRCC enriched in PD-1 signaling, immune system, and cytokine signaling in the immune system, whereas TCA cycle and respiratory, signaling by insulin receptor, and metabolism were enriched in chRCC. Feature selection based on Decision Tree Classifier revealed that the model with two genes, including NDUFA4L2 and DAT, had an accuracy of 98.89%. Supervised classification models based on H-score of NDUFA4L2, and DAT revealed that Decision Tree models showed the best performance with 82% accuracy and 0.9 AUC. NDUFA4L2 expression was associated with lymphovascular invasion, pathologic stage and pT stage in ccRCC. Using integrated bioinformatics and machine learning analysis, NDUFA4L2 and DAT were identified as novel biomarkers to differential diagnosis ccRCC from non-ccRCC., Competing Interests: The authors affirm that there are no conflicts of interest, and all authors attest to the accuracy of the information presented., (Copyright: © 2024 Panwoon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown., Methods: Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration., Results: It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments., Conclusions: Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs., (© 2024. The Author(s).)

A recent study described a rare subtype of tuberous sclerosis complex ( TSC )-mutated renal cell carcinoma primarily characterized by Xanthomatous giant cell morphology. Only 2 cases in young individuals have been reported so far, making the correct diagnosis challenging from a pathological perspective. It remains unknown whether this tumor represents an independent subtype or belongs to other TSC -mutated tumors. We conducted a clinicopathologic evaluation and immunohistochemical profiling of 5 cases of Xanthomatous Giant Cell Renal Cell Carcinoma (XGC RCC) with confirmed TSC2 mutations through targeted DNA sequencing. In addition, we analyzed transcriptomic profiles using RNA-seq for the following samples: XGC RCC, Low-grade Oncocytic tumors (LOT), High-grade Oncocytic tumors/Eosinophilic Vacuolar Tumors (HOT/EVT), Eosinophilic Solid and Cystic Renal Cell Carcinomas (ESC RCC), Chromophobe cell Renal Cell Carcinomas (ChRCC), Renal Oncocytomas (RO), clear cell Renal Cell Carcinomas (ccRCC), and normal renal tissues. There were 2 female and 3 male patients, aged 22 to 58 years, who underwent radical nephrectomy for tumor removal. The tumor sizes ranged from 4.7 to 9.5 cm in diameter. These tumors exhibited ill-defined boundaries, showed an expansive growth pattern, and featured distinctive tumor giant cells with abundant eosinophilic to Xanthomatous cytoplasm and prominent nucleoli. All tumors had low Ki-67 proliferation indices (<1%) and demonstrated immune reactivity for CD10, PAX8, CK20, CathepsinK, and GPNMB. Next-generation sequencing confirmed TSC2 mutations in all cases. RNA sequencing-based clustering indicated a close similarity between the tumor and ESC RCC. One patient (1/5) died of an accident 63 months later, while the remaining patients (4/5) were alive without tumor recurrences or metastases at the time of analysis, with a mean follow-up duration of 43.4 months. Our research supports the concept that Xanthomatous giant cell renal cell carcinoma (XGC RCC) shares clinicopathological and molecular characteristics with ESC RCC and shows a relatively positive prognosis, providing further support for a close morphologic spectrum between the two. We propose considering XGC RCC as a distinct subtype of ESC RCC., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The role of disulfidptosis in kidney renal clear cell carcinoma (KIRC) remains unknown. This study investigated disulfidptosis-related biomarkers for KIRC prognosis prediction and individualized treatment. KIRC patients were clustered by disulfidptosis profiles. Differential expression analysis, survival models, and machine learning were used to construct the disulfidptosis-related prognostic signature (DRPS). Characterizations of the tumor immune microenvironment, genetic drivers, drug sensitivity, and immunotherapy response were explored according to the DRPS risk stratification. Markers included in the signature were validated using single-cell, spatial transcriptomics, quantitative RT-qPCR, and immunohistochemistry. In the discovery cohort, we unveiled two clusters of KIRC patients that differed significantly in disulfidptosis regulator expressions and overall survival (OS). After multiple feature selection steps, a DRPS prognostic model with four features (CHAC1, COL7A1, FOXM1, SHOX2) was constructed and validated. Combined with clinical factors, the model demonstrated robust performance in the discovery and external validation cohorts (5-year AUC = 0.793 and 0.846, respectively). KIRC patients with high-risk scores are characterized by inferior OS, less tumor purity, and increased infiltrations of fibroblasts, M1 macrophages, and B cells. High-risk patients also have higher frequencies of BAP1 and AHNAK2 mutation. Besides, the correlation between the DRPS score and the chemotherapy-response signature indicated the potential effect of Gefitinib for high-risk patients. Among the signature genes, FOXM1 is highly expressed in cycling tumor cells and exhibits spatial aggregation, while others are expressed sparsely within tumor samples. The DRPS model enables improved clinical management and personalized KIRC therapy. The identified biomarkers and immune characteristics offer new mechanistic insight into disulfidptosis in KIRC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of kidney cancer. Many patients are diagnosed at advanced stages, making early detection crucial. Unfortunately, there are currently no noninvasive tests for ccRCC, emphasizing the need for new biomarkers. Additionally, ccRCC often develops resistance to treatments like radiotherapy and chemotherapy. Identifying biomarkers that predict treatment outcomes is vital for personalized care. The integration of artificial intelligence (AI), multi-omics analysis, and computational biology holds promise in bolstering detection precision and resilience, opening avenues for future investigations. The amalgamation of radiogenomics and biomaterial-basedimmunomodulation signifies a revolutionary breakthrough in diagnostic medicine. This review summarizes existing literature and highlights emerging biomarkers that enhance diagnostic, predictive, and prognostic capabilities for ccRCC, setting the stage for future clinical research., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)