Clear Cell Carcinoma Of Kidney Research Articles

Bioinformatics analysis and experimental validation of m6A and cuproptosis-related lncRNA NFE4 in clear cell renal cell carcinoma

PurposeThis study aimed to construct an m6A and cuproptosis-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using the information acquired from The Cancer Genome Atlas (TCGA) database.MethodsFirst, the co-expression analysis was performed to identify lncRNAs linked with N6-methyladenosine (m6A) and cuproptosis in ccRCC. Then, a model encompassing four candidate lncRNAs was constructed via univariate, least absolute shrinkage together with selection operator (LASSO), and multivariate regression analyses. Furthermore, Kaplan–Meier, principal component, functional enrichment annotation, and nomogram analyses were performed to develop a risk model that could effectively assess medical outcomes for ccRCC cases. Moreover, the cellular function of NFE4 in Caki-1/OS-RC-2 cultures was elucidated through CCK-8/EdU assessments and Transwell experiments. Dataset outcomes indicated that NFE4 can have possible implications in m6A and cuproptosis, and may promote ccRCC progression.ResultsWe constructed a panel of m6A and cuproptosis-related lncRNAs to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. Furthermore, the m6A and cuproptosis-related lncRNA model indicated higher diagnostic efficiency than other clinical features. Moreover, the NFE4 function analysis indicated a gene associated with m6A and cuproptosis-related lncRNAs in ccRCC. It was also revealed that the proliferation and migration of Caki-1 /OS-RC-2 cells were inhibited in the NFE4 knockdown group.ConclusionOverall, this study indicated that NFE4 and our constructed risk signature could predict outcomes and have potential clinical value.

Assessing the role of programmed cell death signatures and related gene TOP2A in progression and prognostic prediction of clear cell renal cell carcinoma

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.

Mechanism of lncRNA SNHG16 on kidney clear cell carcinoma cells by targeting miR-506-3p/ETS1/RAS/ERK molecular axis

ObjectiveThis study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future. MethodsThirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior. ResultsSNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P < 0.05). After SNHG16 silence, KIRC cells showed decreased proliferation, invasion and migration capabilities and increased apoptosis rate; correspondingly, increase in SNHG16 expression achieved opposite results (P < 0.05). Finally, in the rescue experiment, the effects of elevated SNHG16 on KIRC cells were reversed by simultaneous increase in miR-506-3p, and the effects of miR-506-3p were reversed by ETS1. Activation of the RAS/ERK pathway had the same effect as increase in ETS1, which further worsened the malignancy of KIRC. After miR-506-3p increase and ETS1 silence, the RAS/ERK signaling pathway was inhibited (P < 0.05). At last, the rescue experiment (co-transfection) confirmed that the effect of SNHG16 on KIRC cells is achieved via the miR-506-3p/ETS1/RAS/ERK molecular axis. ConclusionSNHG16 regulates the biological behavior of KIRC cells by targeting the miR-506-3p/ETS1/RAS/ERK molecular axis.

ZDHHC3-mediated S-palmitoylation of SLC9A2 regulates apoptosis in kidney clear cell carcinoma

PurposeKidney clear cell carcinoma (KIRC) has a poor prognosis, high morbidity and mortality rates, and high invasion and metastasis rate, and effective therapeutic targets are lacking. zDHHC3 has been implicated in various cancers, but its specific role in KIRC remains unclear.MethodsIn this study, we performed a pan-cancer analysis, bioinformatics analysis, and cell experiment to detect the role of zDHHC3 in KIRC.ResultszDHHC3 was significantly down-regulated in KIRC, and that its high expression was associated with favorable patient outcomes. We identified 202 hub genes that were most relevant to high zDHHC3 expression and KIRC, and found that they were involved mainly in ion transport and renal cell carcinoma. Among these hub genes, SLC9A2 was identified as a downstream gene of zDHHC3. zDHHC3 suppression led to decreased expression and S-palmitoylation of SLC9A2, which further inhibited the apoptosis of Caki-2 cells.ConclusionOur findings suggest that zDHHC3 plays an important role in KIRC, due partly to its regulation of SLC9A2 S-palmitoylation. The targeting of the zDHHC3–SLC9A2 axis may provide a new option for the clinical treatment of KIRC.

Pan-cancer analysis reveals potential immunological and prognostic roles of METTL7A in human cancers

Methyltransferase-like protein 7A (METTL7A) is an m6A RNA methyltransferase that has been linked to cancer prognosis and drug resistance. However, a comprehensive analysis of METTL7A is lacking. The expression of METTL7A, prognostic performance, correlation with microsatellite instability (MSI), tumor mutational burden (TMB), and immune infiltration was investigated in The Cancer Genome Atlas (TCGA). Immunohistochemistry staining was applied to detect METTL7A in 6 tumors. METTL7A was significantly decreased in 19 cancers in TCGA including LUAD. Alterations of METTL7A include amplification and mutation, and epigenetic alterations revealed increased promoter methylation may result in down-regulation of METTL7A in LUAD. We also found that METTL7A was linked to both TMB and MSI in LUAD. METTL7A was increasingly correlated with invasive immune cells, while being negatively associated with Macrophages M0, Mast cells activated, activated memory CD4 T cells, CD8 T cells, and follicular helper T cells in several tumors. Additionally, METTL7A showed similar correlation with immune therapy-related genes across cancers. Our biological validation found that the protein levels of METTL7A were down-regulated in breast cancer (BRCA), endometrioid cancer (UCEC), colon cancer (COAD), prostate cancer (PRAD), and kidney clear cell carcinoma (KIRC), as detected by immunohistochemistry staining. Overall, our work indicates that METTL7A may serve as promising diagnostic and prognostic indicator of LUAD, and our work sheds light on the potential immunological and prognostic roles of METTL7A in human cancers.

Systematic pan-cancer analyses of the potential function of the Golgi scaffold protein PAQR3

Progesterone and AdipoQ Receptor 3 (PAQR3) is a member of the AdipoQ receptor. Our previous studies have found that PAQR3 plays a role as a candidate inhibitor in cardiac adenocarcinoma, breast cancer, gastric cancer and colorectal cancer, but the systematic analysis of PAQR3 in tumors is currently lacking. The objective of this study was to investigate the prognostic and therapeutic value of PAQR3 in 31 tumors. Through the analysis of TCGA, UALCAN, GEO, GEPIA2, TIMER, Kaplan–Meier plotter, TISIDB and other databases, it was found that the expression level of PAQR3 changed significantly in different tumor types, and the expression level of Neuroblastoma was very high. And the level of Prostate adenocarcinoma is low. In addition, the expression level of PAQR3 in Cholangiocarcinoma, Esophageal carcinoma, Head and neck squamous carcinoma, Liver Hepatocellular Carcinoma, Lung Adenocarcinoma and Lung squamous cell carcinoma was significantly higher than that in normal tissues. However, the expression level of PAQR3 in Breast Cancer, Kidney Renal Clear Cell Carcinoma, Kidney renal papillary cell carcinoma, Prostate Adenocarcinoma, Rectum Adenocarcinoma, Thyroid Cancer and Uterine Corpus Endometrial Carcinoma was lower than that in normal tissues. Subsequently, we explored the value of PAQR3 as a prognostic indicator of cancer. In Acute Myeloid Leukemia, Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Kidney Chromophobe, and Thyroid Cancer, PAQR3 expression was positively correlated with OS and DSS, while in Rectum Adenocarcinoma, PAQR3 expression was negatively correlated with OS. PAQR3 high expression group Lower-grade Glioma and Glioblastoma, Pediatric Low-grade Gliomas, Uveal Melanoma, Kidney Chromophobe and DFI were positively correlated. PAQR3 can be used as a risk factor for the prognosis of multiple tumors. Then, we discussed the correlation between PAQR3 and immunology, and found that PAQR3 has a wide range of mutations in various tumor types, the most common mutation type is missense mutation, and common mutation types also include amplification, depth deletion, splicing, truncation and structural variation. Among the tumor samples with PAQR3 alterations, mutation occurred in all tumor samples except prostate adenocarcinoma and adrenal cortical carcinoma, head and neck squamous cell carcinoma, brain low-grade glioma, and kidney clear cell carcinoma, while esophageal adenocarcinoma had the highest total alteration frequency. PAQR3 was strongly associated with CNV in 18 tumors, particularly in Ovarian cancer, Lung squamous cell carcinoma, and Adenoid cystic carcinoma. On the other hand, PAQR3 has a higher SNV frequency in Uterine Corpus Endometrial Carcinoma, Skin Cutaneous Melanoma and Lung Adenocarcinoma, among which Uterine Corpus Endometrial Carcinoma has the highest SNV frequency. These results showed that PAQR3 expression levels were significantly correlated with tumor mutation load, microsatellite instability, neoantigens, and purity. In summary, PAQR3 can affect the tumor microenvironment and has potential for chemotherapy. Finally, we investigated the role of PAQR3 in tumor resistance and found that the expression of PAQR3 affects the efficacy of multiple chemotherapy drugs. Based on these studies, we found that PAQR3 plays an important role in cancer and has potential in tumor diagnosis and prognosis.

Establishment and validation of a novel peroxisome-related gene prognostic risk model in kidney clear cell carcinoma

BackgroundKidney clear cell carcinoma (KIRC) is the most common subtype of renal cell carcinoma. Peroxisomes play a role in the regulation of tumorigenesis and cancer progression, yet the prognostic significance of peroxisome-related genes (PRGs) remains rarely studied. The study aimed to establish a novel prognostic risk model and identify potential biomarkers in KIRC.MethodsThe significant prognostic PRGs were screened through differential and Cox regression analyses, and LASSO Cox regression analysis was performed to establish a prognostic risk model in the training cohort, which was validated internally in the testing and entire cohorts, and further assessed in the GSE22541 cohort. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the function and pathway differences between the high-risk and low-risk groups. The relationship between risk score and immune cell infiltration levels was evaluated in the CIBERSORT, ESTIMATE and TIMER databases. Finally, potential biomarkers were identified and validated from model genes, using immunohistochemistry.ResultsFourteen significant prognostic PRGs were identified using multiple analyses, and 9 genes (ABCD1, ACAD11, ACAT1, AGXT, DAO, EPHX2, FNDC5, HAO1, and HNGCLL1) were obtained to establish a prognostic model via LASSO Cox regression analysis. Combining the risk score with clinical factors to construct a nomogram, which provided support for personalized treatment protocols for KIRC patients. GO and KEGG analyses highlighted associations with substance metabolism, transport, and the PPAR signaling pathways. Tumor immune infiltration indicated immune suppression in the high-risk group, accompanied by higher tumor purity and the expression of 9 model genes was positively correlated with the level of immune cell infiltration. ACAT1 has superior prognostic capabilities in predicting the outcomes of KIRC patients.ConclusionsThe peroxisome-related prognostic risk model could better predict prognosis in KIRC patients.

LRP6 is a potential biomarker of kidney clear cell carcinoma related to prognosis and immune infiltration.

Renal cell carcinoma is the most common and most lethal genitourinary tumor. The causes of renal clear cell carcinoma are complex and the heterogeneity of the tumor tissue is high, so patient outcomes are not very satisfactory. Exploring biomarkers in the progression of renal clear cell carcinoma is crucial to improve the diagnosis and guide the treatment of renal clear cell carcinoma. LRP6 is a co-receptor of the Wnt/β-catenin signaling pathway, which is involved in cell growth, inflammation and cell transformation through activation of the Wnt/β-catenin signaling pathway. Abnormal expression of LRP6 is associated with the malignant phenotype, metastatic potential and poor prognosis of various tumors. In this study, we found that LRP6 was abnormally highly expressed in a variety of tumors and significantly correlated with microsatellite instability, tumor mutation burden, and immune cell infiltration and immune checkpoint expression in a variety of tumors. Moreover, we found that LRP6 was significantly associated with the prognosis of renal clear cell carcinoma. Further we found a significant correlation between LRP6 and the expression of m6A-related genes and ferroptosis-related genes. Finally, we also found a significant correlation between the expression of LRP6 and the sensitivity to common drugs used in kidney clear cell carcinoma treatment. These results suggest that LRP6 is likely to be a potential target for kidney clear cell carcinoma treatment.

Pan-Cancer Analysis of P3H1 and Experimental Validation in Renal Clear Cell Carcinoma.

Prolyl 3-hydroxylase 1 (P3H1) has been implicated in cancer development, but no pan-cancer analysis has been conducted on P3H1. In this study, for the first time, aspects associated with P3H1, such as the mRNA expression, any mutation, promoter methylation, and prognostic significance, the relationship between P3H1 and clinicopathological parameters, drug sensitivity, and immune cell infiltration were investigated by searching several databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), cBioPortal, and The Tumor Immune Evaluation Resource (TIMER2.0) using bioinformatics tools. The findings indicate significant differential expression of P3H1 in most tumors when compared to normal tissues, with a strong association with clinical prognosis. A pan-cancer Cox regression analysis revealed that high P3H1 expression is significantly associated with low overall survival in patients with brain lower grade glioma, kidney clear cell carcinoma, adrenocortical cancer, liver hepatocellular carcinoma, mesothelioma, sarcoma, uveal melanoma, bladder urothelial carcinoma, kidney papillary cell carcinoma, kidney chromophobe, thymoma, and thyroid carcinoma. A negative correlation was observed between P3H1 DNA methylation and its expression. P3H1 is significantly associated with infiltrating cells, immune-related genes, tumor mutation burden, microsatellite instability, and mismatch repair. Finally, A significant correlation was found between P3H1 expression and sensitivity to nine drugs. Thus, enhanced P3H1 expression is associated with poor prognosis in a variety of tumors, which may be due to its role in tumor immune regulation and tumor microenvironment. This pan-cancer analysis provides insight into the function of P3H1 in tumorigenesis of different cancers and provides a theoretical basis for further in-depth studies to follow.

Creating and Utilizing an Immune-Related Gene Prognosis Framework for Kidney Clear Cell Carcinoma

Creating and Utilizing an Immune-Related Gene Prognosis Framework for Kidney Clear Cell Carcinoma

Differential Expression Analysis Based on Ensemble Strategy on miRNA Profiles of Kidney Clear Cell Carcinoma.

Kidney clear cell carcinoma (KIRC) is the most common type of kidney cancer, accounting for approximately 60-85% of all the kidney cancers. However, there are few options available for early treatment. Therefore, it is extremely important to identify biomarkers and study therapeutic targets for KIRC. Since there are few studies on KIRC, we used a data-driven approach to identify differential genes. Here, we used miRNA gene expression profile data from the TCGA database species of KIRC and proposed a machine learning-based approach to quantify the importance score of each gene. Then, an ensemble method was utilized to find the optimal subset of genes used to predict KIRC by clustering. The most genetic subset was then used to classify and predict KIRC. Differential genes were screened by several traditional differential analysis methods, and the selected gene subset showed a better performance. Independent testing sets from the GEO database were used to verify the effectiveness of the optimal subset of genes. Besides, cross-validation was made to verify the effectiveness of the approach. Finally, important genes, such as miR-140 and miR-210, were found to be involved in the biochemical processes of KIRC, which also proved the effectiveness of our approach.

An immunogenic cell death-related classification predicts prognosis and response to immunotherapy in kidney renal clear cell carcinoma.

Immunogenic cell death (ICD) is a form of regulated cell death that activates an adaptive immune response in an immunocompetent host and is particularly sensitive to antigens from tumor cells. Kidney clear cell carcinoma (KIRC) is an immunogenic tumor with extensive tumor heterogeneity. However, no reliable predictive biomarkers have been identified to reflect the immune microenvironment and therapeutic response of KIRC. Therefore, we used the CIBERSORT and ESTIMATE algorithms to define three ICD clusters based on the expression of ICD-related genes in 661 KIRC patients. Subsequently, we identified three different ICD gene clusters based on the overlap of differentially expressed genes (DEGs) within the ICD clusters. In addition, principal component analysis (PCA) was performed to calculate the ICD scores. The results showed that patients with reduced ICD scores had a poorer prognosis and reduced transcript levels of immune checkpoint genes regulated with T cell differentiation. Furthermore, the ICD score was negatively correlated with the tumor mutation burden (TMB) value of KICD. patients with higher ICD scores showed clinical benefits and advantages of immunotherapy, indicating that the ICD score is an accurate and valid predictor to assess the effect of immunotherapy. Overall, our study presents a comprehensive KICD immune-related ICD landscape that can provide guidance for current immunotherapy and predict patient prognosis to help physicians make judgments about the patient's disease and treatment modalities, and can guide current research on immunotherapy strategies for KICD.

Mucin-poor mucinous tubular and spindle cell kidney cancer and clear cell renal cell carcinoma: a rare clinical case

Mucinous tubular and spindle cell carcinoma of the kidney is a rare low-grade malignant tumour and accounts for less than 1% of all renal neoplasms. The classic morphological structure of the tumor is represented by three elements: spindle cells, ducts and myxoid or mucinous stroma. This tumor is indolent with a low risk of metastasis and a favorable outcome. However, cases with relapses, metastases to regional lymph nodes, and distant metastases, which were mainly characterised by high nuclear atypia, sarcomatoid transformation and other atypical morphological features are described in the literature. Several cases of mucin-poor and mucin-free mucinous tubular and spindle cell renal cell carcinoma have also been presented, making it difficult to differentiate from other renal cell carcinomas. There are reports of cases of mucin poor mucinous tubular and spindle cell carcinoma, which were accompanied by relapses and metastases. Thus, although the tumour is indolent, careful follow-up is necessary even after radical excision. In this article, we report a rare clinical case of combination of mucin-poor mucinous tubular and spindle cell carcinoma and clear cell renal cell carcinoma of the kidney in a 50-year-old man. The results of clinical and instrumental studies, as well as the morphological features of both tumors are presented. Due to the atypical morphological structure of mucinous tubular and spindle cell carcinoma, the final diagnosis was possible using an immunohistochemical method, which demonstrated the immunohistochemical profile characteristic of this tumour.

Prognostic value and immunological function of disulfidptosis regulator LRPPRC in kidney clear cell carcinoma

Prognostic value and immunological function of disulfidptosis regulator LRPPRC in kidney clear cell carcinoma

The clinicopathological and prognostic significances of EZH2 expression in urological cancers: A meta‑analysis and bioinformatics analysis.

The Drosophila zeste enhancer homolog 2 gene (enhancer of zeste homolog 2; EZH2) is an important member of the polycomb group (PcG) gene family, which maintains the homologous gene via chromosome modification during embryonic development. EZH2 is overexpressed in various tumors, is closely related to tumor formation and growth, and has a malignant phenotype that promotes tumor cell proliferation, proliferation and metastasis. In the present study, a meta- and bioinformatic analysis was performed using data from multiple online databases until August 30, 2022. EZH2 upregulation was found in kidney, bladder and prostate cancers. EZH2 expression was negatively related to TNM staging and pathological grade in kidney and prostate cancers (P<0.05), as well as invasion depth and pathological grade in bladder cancer. According to the KM-plotter database, EZH2 expression was inversely associated with poor overall survival in patients with kidney clear cell renal cell carcinoma (RCC) and papillary RCC and with favorable survival in bladder cancer. EZH2 expression was negatively related to relapse-free survival in kidney papillary RCC and bladder cancer but positively associated with kidney clear cell RCC. According to GEPIA and UALCAN databases, EZH2 expression was higher in tumor tissue than normal tissue. The TIMER database showed that EZH2 was closely associated with the proportion of seven immune cell infiltrates in kidney, bladder, and prostate cancers. High EZH2 expression may be a potential marker of tumorigenesis and metastasis in patients with urological cancers.

Genetically predicted vitamin C levels significantly affect patient survival and immunotypes in multiple cancer types.

Recent observational studies and meta-analyses have shown that vitamin C reduces cancer incidence and mortality, but the underlying mechanisms remain unclear. We conducted a comprehensive pan-cancer analysis and biological validation in clinical samples and animal tumor xenografts to understand its prognostic value and association with immune characteristics in various cancers. We used the Cancer Genome Atlas gene expression data involving 5769 patients and 20 cancer types. Vitamin C index (VCI) was calculated using the expression of 11 genes known to genetically predict vitamin C levels, which were classified into high and low subgroups. The correlation between VCI and patient overall survival (OS), tumor mutational burden (TMB), microsatellite instability (MSI), and immune microenvironment was evaluated, using Kaplan-Meier analysis method and ESTIMATE (https://bioinformatics.mdanderson.org/estimate/). Clinical samples of breast cancer and normal tissues were used to validate the expression of VCI-related genes, and animal experiments were conducted to test the impact of vitamin C on colon cancer growth and immune cell infiltration. Significant changes in expression of VCI-predicted genes were observed in multiple cancer types, especially in breast cancer. There was a correlation of VCI with prognosis in all samples (adjusted hazard ratio [AHR] = 0.87; 95% confidence interval [CI] = 0.78-0.98; P = 0.02). The specific cancer types that exhibited significant correlation between VCI and OS included breast cancer (AHR = 0.14; 95% CI = 0.05-0.40; P < 0.01), head and neck squamous cell carcinoma (AHR = 0.20; 95% CI = 0.07-0.59; P < 0.01), kidney clear cell carcinoma (AHR = 0.66; 95% CI = 0.48-0.92; P = 0.01), and rectum adenocarcinoma (AHR = 0.01; 95% CI = 0.001-0.38; P = 0.02). Interestingly, VCI was correlated with altered immunotypes and associated with TMB and MSI negatively in colon and rectal adenocarcinoma (P < 0.001) but positively in lung squamous cell carcinoma (P < 0.05). In vivo study using mice bearing colon cancer xenografts demonstrated that vitamin C could inhibit tumor growth with significant impact on immune cell infiltration. VCI is significantly correlated with OS and immunotypes in multiple cancers, and vitamin C might have therapeutic potential in colon cancer.

Identification of berberine as a potential therapeutic strategy for kidney clear cell carcinoma and COVID-19 based on analysis of large-scale datasets.

Regarding the global coronavirus disease 2019 (COVID)-19 pandemic, kidney clear cell carcinoma (KIRC) has acquired a higher infection probability and may induce fatal complications and death following COVID-19 infection. However, effective treatment strategies remain unavailable. Berberine exhibits significant antiviral and antitumour effects. Thus, this study aimed to provide a promising and reliable therapeutic strategy for clinical decision-making by exploring the therapeutic mechanism of berberine against KIRC/COVID-19. Based on large-scale data analysis, the target genes, clinical risk, and immune and pharmacological mechanisms of berberine against KIRC/COVID-19 were systematically investigated. In total, 1,038 and 12,992 differentially expressed genes (DEGs) of COVID-19 and KIRC, respectively, were verified from Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively, and 489 berberine target genes were obtained from official websites. After intersecting, 26 genes were considered potential berberine therapeutic targets for KIRC/COVID-19. Berberine mechanism of action against KIRC/COVID-19 was revealed by protein-protein interaction, gene ontology, and Kyoto Encyclopedia of Genes and Genomes with terms including protein interaction, cell proliferation, viral carcinogenesis, and the PI3K/Akt signalling pathway. In COVID-19 patients, ACOX1, LRRK2, MMP8, SLC1A3, CPT1A, H2AC11, H4C8, and SLC1A3 were closely related to disease severity, and the general survival of KIRC patients was closely related to ACOX1, APP, CPT1A, PLK1, and TYMS. Additionally, the risk signature accurately and sensitively depicted the overall survival and patient survival status for KIRC. Numerous neutrophils were enriched in the immune system of COVID-19 patients, and the lives of KIRC patients were endangered due to significant immune cell infiltration. Molecular docking studies indicated that berberine binds strongly to target proteins. This study demonstrated berberine as a potential treatment option in pharmacological, immunological, and clinical practice. Moreover, its therapeutic effects may provide potential and reliable treatment options for patients with KIRC/COVID-19.

Prognostic Role of Long-Chain Acyl-Coenzyme A Synthetase Family Genes in Patients with Clear Cell Renal Cell Carcinoma: A Comprehensive Bioinformatics Analysis Confirmed with External Validation Cohorts

We aimed to determine the prognostic role of long-chain acyl-CoA synthetases (ACSLs) as a disease marker for kidney clear cell carcinoma (KIRC). The Cancer Genome Atlas (TCGA) data were accessed via open access LinkedOmics database for KIRC. Provisional datasets were used for analysis as previously described and gene expression quantification data were downloaded. The corresponding clinical information of patients also were obtained from the database. Five ACSL family members, ACSL1, ACSL3, ACSL4, ACSL5, and ACSL6, were investigated in the TCGA-KIRC cohort. Xena browser, cBioPortal and UALCAN, and Cancer Cell Line Encyclopedia (CCLE) databases were also used to confirm the results. External validation was performed using patient cohorts from the Gene Expression Omnibus (GEO-NCBI) database. Finally, the protein-protein interaction (PPI) was constructed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape software. Pathological T3-T4 stage tumors had significantly lower ACSL1 mRNA expression (P=.009). Patients with pathologically confirmed metastasis exhibited significantly lower expression, as well (P=.02). ACSL1 mRNA expression was associated with overall survival (OS) and negatively correlated with OS time. Univariate and multivariate analyses showed that lower ACSL1 mRNA expression level was associated with mortality. Moreover, ACSL1 mRNA expression was exhibited significant difference in some VHL gene region mutations and PBRM1_p.R1010 mutation, and negatively correlated with HIF1-alpha mRNA expression (P < .001). Confirmatory analyses and external validation also revealed similar findings. Lowered ACSL1 mRNA expression is associated with worse tumor histopathology and poor overall survival in KIRC. It may be used for prognostic marker for KIRC.

Relationship between body composition and PBRM1 mutations in clear cell renal cell carcinoma: a propensity score matching analysis

This study aimed to examine the relationship between body muscle and adipose tissue composition in clear cell renal cell carcinoma patients with PBRM1 gene mutation. Cancer Genome Atlas Kidney clear cell renal cell carcinoma and Clinical Proteomic Tumor Analysis Consortium clear cell renal cell carcinoma collections were retrieved from the Cancer Imaging Archive. A total of 291 clear cell renal cell carcinoma patients were included in the study retrospectively. Patients' characteristics were obtained from Cancer Imaging Archive. Body composition was assessed with abdominal computed tomography using the automated artificial intelligence software (AID-U™, iAID Inc., Seoul, Korea). Body composition parameters of the patients were calculated. To investigate the net effect of body composition, the propensity score matching procedure was applied over age, gender, and T-stage parameters. Of the patients, 184 were males and 107 were females. Mutations in the PBRM1 gene were detected in 77 of the patients. While there was no difference in adipose tissue areas between the PBRM1 mutation group and those without PBRM1 mutation, statistically significant differences were found in normal attenuated muscle area parameters. This study shows that there was no difference between adipose tissue areas in patients with PBMR1 mutation, but normal attenuated muscle area was found to be higher in PBRM1 patients.

High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma

Invasion and metastasis led to poor prognosis and death of clear cell renal cell carcinoma (ccRCC) patients. The deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) was reported to promote multiple tumor progression. However, there is no research about DNTTIP1 in ccRCC. Kaplan-Meier survival analysis, multivariate analysis demonstrated the prognostic indicator in overall survival (OS) and disease-free survival (DFS) of ccRCC with DNTTIP1 expression in the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC). Receiver operator characteristic (ROC) curve analyzed diagnostic ability of DNTTIP1 in TCGA-KIRC and validation dataset. The quantitative real-time polymerase chain reaction (qRT-PCR) detected the DNTTIP1 expression in renal cancer tissues, and the Office of Cancer Clinical Proteomics Research (CPTAC) verified the protein expression of DNTTIP1. Moreover, nomogram predicted the role of DNTTIP1 in ccRCC patient. Single-sample Gene Set Enrichment Analysis (SsGSEA) and GSEA evaluated the pathogenesis role of DNTTIP1 in TCGA-KIRC. DNTTIP1 expression was higher in ccRCC tumor tissues. High expression of DNTTIP1 was associated with poor OS (HR = 1.618, P < 0.0001), and poor DFS (HR = 1.789, P < 0.0001). SsGSEA and GSEA showed DNTTIP1 was associated with hypoxia, epithelial-mesenchymal transition (EMT), angiogenesis, G2M checkpoint. DNTTIP1 had a positive correlation with EMT biomarkers in ccRCC, and might be an effective target for ccRCC. This study provided that higher expression of DNTTIP1 predicted poor prognosis in ccRCC, and DNTTIP1 might be a novel detection biomarker and therapeutic target of tumor malignant in the future.