Kidney clear cell carcinoma (KIRC) commonly presents with metastases upon diagnosis, highlighting the critical need to identify more precise biomarkers for early detection, intervention, and personalized treatment. Although The REEP family has been investigated in cancer development, the specific relationship between REEP4 and cancer remains unclear. In our study, we employed bioinformatics analysis and conducted fundamental experiments to evaluate the potential of REEP4 as a biomarker for predicting the prognosis and therapeutic efficacy of KIRC. Comparing KIRC tumor tissues to normal tissues, we observed a significant upregulation in REEP4 expression, with higher levels of REEP4 correlating positively with tumor malignancy. Further COX regression analysis, as well as single and multifactorial analyses, confirmed that high REEP4 expression indicated lower survival rates in KIRC. Gene function analysis also identified associations between REEP4 and critical pathways such as the cell cycle, along with its involvement in protein binding. Furthermore, our investigation of the immune response suggests that a favorable immunotherapeutic response is linked to a reduction in REEP4 expression. Subsequently, we conducted in vitro experiments to confirm the overexpression of REEP4 in KIRC tumor tissues and renal cancer cells. In summary, our study revealed a close association between REEP4 expression and KIRC, emphasizing its correlation with prognosis and the immune response. These findings suggest that REEP4 is a potential biomarker for KIRC.

UNASSIGNED: Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that seriously threatens human health. Rho GTPase-activating protein 4 (ARHGAP4) plays an important role in the occurrence and development of tumors.
UNASSIGNED: The purpose of this study was to explore the role of ARHGAP4 in the progression of KIRC and its diagnostic and prognostic value.
UNASSIGNED: Multiple analytical methods and in vitro cell assays were used to explore the expression of ARHGAP4 and its value in the progression, diagnosis and prognosis of KIRC. The biological function of ARHGAP4 was studied by GO analysis and KEGG pathway analysis, and then the relationship between ARHGAP4 and immune infiltration was analyzed.
UNASSIGNED: The expression of ARHGAP4 was significantly up-regulated in KIRC. We found that the high expression of ARHGAP4 was related to the progression of KIRC and suggested a poor prognosis. Compared with normal tissues, ARHGAP4 had a better diagnostic value in KIRC. The biological function of ARHGAP4 was related to immunity, and its expression was also closely related to tumor immune infiltration and immune checkpoints.
UNASSIGNED: Our study demonstrated that ARHGAP4 may be a biomarker, which is related to the progression, diagnosis and prognosis of KIRC. Its biological functions are related to tumor immune infiltration.

Troponin T1 (TNNT1) plays a crucial role in muscle contraction but its role in cancer, particularly in kidney renal clear cell carcinoma (KIRC), is not well-understood. This study explores the expression, clinical significance and biological functions of TNNT1 in various cancers, with an emphasis on its involvement in KIRC. We analysed TNNT1 expression in cancers using databases like TCGA and GTEx, assessing its prognostic value, mutation patterns, methylation status and functional implications. The study also examined TNNT1\'s effect on the tumour microenvironment and drug sensitivity in KIRC, complemented by in vitro TNNT1 knockdown experiments in KIRC cells. TNNT1 is overexpressed in several cancers and linked to adverse outcomes, showing frequent upregulation mutations and abnormal methylation. Functionally, TNNT1 connects to muscle and cancer pathways, affects immune infiltration and drug responses, and its overexpression in KIRC is associated with advanced disease and reduced survival. Knocking down TNNT1 curbed KIRC cell growth. TNNT1\'s aberrant expression plays a significant role in tumorigenesis and immune modulation, highlighting its value as a prognostic biomarker and a potential therapeutic target in KIRC and other cancers. Further studies are essential to understand TNNT1\'s oncogenic mechanisms in KIRC.

UNASSIGNED: 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.
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.
CONCLUSIONS: 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.

Kidney renal clear cell carcinoma (KIRC) is a highly immune-infiltrated kidney cancer with the highest mortality rate and the greatest potential for invasion and metastasis. Solute carrier family 11 member1 (SLC11A1) is a phagosomal membrane protein located in monocytes and plays a role in innate immunity, autoimmune diseases, and infection, but its expression and biological role in KIRC is still unknown. In this study, we sought to investigate the potential value of SLC11A1 according to tumor growth and immune response in KIRC. TIMER and UALCAN database was used to analyze the expression feature and prognostic significance of SLC11A1 and its correlation with immune-related biomarkers in KIRC. Proliferation, migration, and invasion were measured using colony formation, EdU, and transwell assays. Role of SLC11A1 on KIRC tumor growth was examined by the xenograft tumor model in vivo. Effects of KIRC cells on macrophage polarization and the proliferation and apoptosis of CD8+ T cells were analyzed using flow cytometry assays. Herein, SLC11A1 was highly expressed in KIRC tissues and cell lines. SLC11A1 downregulation repressed KIRC cell proliferation, migration, invasion, macrophage, and lymphocyte immunity in vitro, as well as hindered tumor growth in vivo. SLC11A1 is significantly correlated with immune cell infiltration and immune-related biomarkers. In KIRC patients, SLC11A1 is highly expressed and positively correlated with the immune-related factors CCL2 and PD-L1. SLC11A1 induced CCL2 and PD-L1 expression, thereby activating the JAK/STAT3 pathway. SLC11A1 deficiency constrained KIRC cell malignant phenotypes and immune response via regulating CCL2 and PD-L1-mediated JAK/STAT3 pathway, providing a promising therapeutic target for KIRC treatment.

Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.

UNASSIGNED: Abnormally expressed Runt-associated transcription factor (RUNX) family has been reported in multiple tumors. Nevertheless, the immunological role of RUNX family in kidney renal clear cell carcinoma (KIRC) remains unknown.
UNASSIGNED: We studied the RNA-seq data regarding tumor and healthy subjects from several public databases in detail for evaluating the prognostic and immunological functions owned by three RUNX genes in cancer patients. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining served for detecting their expressions in tumor and normal samples.
UNASSIGNED: We observed that KIRC patients presented high expressions of RUNX1, RUNX2, and RUNX3. The expressions of three genes were validated by qRT-PCR, which was same as bioinformatical results. Prognostic analysis indicated that the overexpression of RUNX1 and RUNX2 negatively affects the outcomes in patients with KIRC. Related functional predictions indicated that the RUNXs and co-expression genes were significantly related to the immune response pathway. Moreover, three RUNX members were associated with immune infiltration cells and their related gene markers. The expression of RUNX family in several immune cells is positively or negatively correlated, and its dysregulation is obviously associated with the differential distribution of immune cells. RUNX family genes were abnormally expressed in KIRC patients, and were closely related to the crosstalk of immune cells.
UNASSIGNED: Our findings may help to understand the pathogenesis and immunologic roles of the RUNX family in KIRC patients from new perspectives.

Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.

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.

UNASSIGNED: COVID-19 is a severe infectious disease caused by the SARS-CoV-2 virus, and previous studies have shown that patients with kidney renal clear cell carcinoma (KIRC) are more susceptible to SARS-CoV-2 infection than the general population. Nevertheless, their co-pathogenesis remains incompletely elucidated.
UNASSIGNED: We obtained shared genes between these two diseases based on public datasets, constructed a prognostic risk model consisting of hub genes, and validated the accuracy of the model using internal and external validation sets. We further analyzed the immune landscape of the prognostic risk model, investigated the biological functions of the hub genes, and detected their expression in renal cell carcinoma cells using qPCR. Finally, we searched the candidate drugs associated with hub gene-related targets from DSigDB and CellMiner databases.
UNASSIGNED: We obtained 156 shared genes between KIRC and COVID-19 and constructed a prognostic risk model consisting of four hub genes. Both shared genes and hub genes were highly enriched in immune-related functions and pathways. Hub genes were significantly overexpressed in COVID-19 and KIRC. ROC curves, nomograms, etc., showed the reliability and robustness of the risk model, which was validated in both internal and external datasets. Moreover, patients in the high-risk group showed a higher proportion of immune cells, higher expression of immune checkpoint genes, and more active immune-related functions. Finally, we identified promising drugs for COVID-19 and KIRC, such as etoposide, fulvestrant, and topotecan.
UNASSIGNED: This study identified and validated four shared genes for KIRC and COVID-19. These genes are associated with immune functions and may serve as potential prognostic biomarkers for KIRC. The shared pathways and genes may provide new insights for further mechanistic research and treatment of comorbidities.