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1.
Braz. j. biol ; 84: e250575, 2024. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1350309

RESUMO

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.


Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.


Assuntos
Humanos , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Neoplasias Hepáticas , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Regulação para Cima , Proteínas de Ligação a DNA , Variações do Número de Cópias de DNA
2.
Cancer Discov ; 12(5): 1180, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35491620

RESUMO

Combining the live bacterial product CBM588 with checkpoint inhibitors improved progression-free survival.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Ciclopropanos , Feminino , Humanos , Indóis , Masculino , Intervalo Livre de Progressão
3.
Dis Markers ; 2022: 2883029, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35502301

RESUMO

Renal cell carcinoma (RCC) appears to be a high risk of spread. This research investigated the correlation between a different range of clinical features and intraocular metastasis (IOM) in RCC patients and attempted to determine potential risk factors of RCC patients with IOM. In the study, there are a total of 351 patients with RCC that were recruited between May 1994 and May 2016. The differences between RCC patients with IOM and RCC patients with non-IOM (NIOM) were evaluated by the chi-squared test and Student t test. Binary logistic regression analysis was applied to determine risk factors. Finally, the value of diagnosis for RCC patients with IOM was assessed by receiver operating characteristic (ROC) curve analysis. Eighteen individuals were identified with IOM. There were no significant differences that were detected in alkaline phosphatase (AFP), carcinoembryonic antigen (CEA), alkaline phosphatase (ALP), cancer antigen 125 (CA-125), cancer antigen 153 (CA-153), cancer antigen 199 (CA-199), calcium, age, primary tumor site, and histopathological subtypes between the two groups. But there was a difference in terms of gender (P < 0.05). The IOM group exhibited significantly higher neuron-specific enolase (NSE) and lower hemoglobin (Hb) values compared to the NIOM group (P < 0.05, respectively). Binary logistic regression identified NSE and Hb as significant risk factors of IOM for RCC patient (P < 0.05 and P < 0.001, respectively). The ROC curve analysis indicated that the area under the curve (AUC) values of NSE and Hb were 0.694 and 0.749, while cut-off values were 49.5 ng/mL and 102.5 g/L, respectively. The sensitivity and specificity of NSE were 72.2% and 66.4%, respectively, while those of Hb were 72.2% and 74.2%, respectively. The result reveals that NSE and Hb represent promising significant risk factors of IOM for RCC patients. Notably, Hb is more reliable than NSE in distinguishing case of IOM from NIOM in patients with RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Fosfatase Alcalina , Antígenos de Neoplasias , Biomarcadores Tumorais , Feminino , Hemoglobina Falciforme , Hemoglobinas , Humanos , Masculino , Fosfopiruvato Hidratase , Fatores de Risco
4.
Bioengineered ; 13(4): 11187-11207, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35510387

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas, with high mortality and poor prognoses worldwide. Succinate dehydrogenase (SDH) consists of four nuclear-encoded subunits and it is the only complex involved in both the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). Previous studies have shown decreased SDH activity in ccRCC. However, the role and underlying molecular mechanisms of SDH in ccRCC initiation and development remain unclear. In the present study, pan-cancer analysis of SDH gene expression was analyzed and the relationship between SDH gene expression and clinicopathological parameters was assessed using different databases. cBioPortal, UACLAN, and Tumor Immune Estimation Resource (TIMER) were subsequently utilized to analyze genetic alterations, methylation, and immune cell infiltration of SDH genes in ccRCC patients. We found SDHs were significantly downregulated in ccRCC tissues and correlated with ccRCC progression. Increased methylation and high SDH promoter mutation rates may be the cause of reduced expression of SDHs in ccRCC. Moreover, the interaction network showed that SDH genes were correlated with ferroptosis-related genes. We further demonstrated that SDH inhibition dampened oxidative phosphorylation, reduced ferroptotic events, and restored ferroptotic cell death, characterized by eliminated mitochondrial ROS levels, decreased cellular ROS and diminished peroxide accumulation. Collectively, this study provides new insights into the regulatory role of SDH in the carcinogenesis and progression of ccRCC, introducing a potential target for advanced antitumor therapy through ferroptosis.


Assuntos
Carcinoma de Células Renais , Ferroptose , Neoplasias Renais , Carcinogênese/genética , Carcinoma de Células Renais/metabolismo , Feminino , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo
5.
Zhonghua Bing Li Xue Za Zhi ; 51(5): 437-443, 2022 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-35511640

RESUMO

Objective: To study the clinicopathological features, immunophenotype, molecular changes, differential diagnosis and prognosis of eosinophilic vacuolated tumor (EVT) of the kidney. Methods: Four cases were collected retrospectively from 2014 to 2020 at Ningbo Diagnostic Pathology Center. The clinicopathologic features and immunophenotypic profile were studied by light microscopy and immunohistochemistry. Targeted next-generation sequencing (NGS) panel was used to detect cancer-associated mutation. Follow-up and literature review were also performed. Results: Among the 4 patients studied,2 were males and 2 were females. The age of the patients ranged from 44 to 63 years (the mean age: 51 years).Tumor size ranged from 1.5 to 4.2 cm (mean: 2.3 cm). Microscopically, tumors were well-circumscribed, unencapsulated. Thick-walled vessels and entrapped renal tubules were found within or at the periphery of the tumors. The tumors were predominantly composed of nest pattern, and focal tubular pattern. The tumor cells exhibited abundant, eosinophilic, granular cytoplasm and conspicuous, large nucleoli. Prominent intracytoplasmic vacuoles were seen. These cytoplasmic vacuoles varied in size and frequently coalesced into a large space. Loose fibromatous or hyaline stroma was focally noted. Immunohistochemically, the tumor cells in all cases exhibited a CD117+/CK7-phenotype. All cases were positive for CD10 and p504s. MTOR, S6 and cathepsin K were positive in 4 cases. TFE3, CA9, Melan A and HMB45 were negative in all cases. SDHB retained expression. NGS demonstrated MTOR mutations in all cases, and TSC2 mutation in 2 cases. Conclusions: EVT is a rarely oncocytic renal tumor with unique morphology, immunohistochemical phenotype, molecular profile and an indolent behavior. Recognition of the characteristics of this novel but rare entity will allow for better classification of renal tumors.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Humanos , Rim/patologia , Neoplasias Renais/patologia , Masculino , Estudos Retrospectivos , Serina-Treonina Quinases TOR/genética
8.
Sci Rep ; 12(1): 7240, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508649

RESUMO

Cancer is among the highly complex disease and renal cell carcinoma is the sixth-leading cause of cancer death. In order to understand complex diseases such as cancer, diabetes and kidney diseases, high-throughput data are generated at large scale and it has helped in the research and diagnostic advancement. However, to unravel the meaningful information from such large datasets for comprehensive and minute understanding of cell phenotypes and disease pathophysiology remains a trivial challenge and also the molecular events leading to disease onset and progression are not well understood. With this goal, we have collected gene expression datasets from publicly available dataset which are for two different stages (I and II) for renal cell carcinoma and furthermore, the TCGA and cBioPortal database have been utilized for clinical relevance understanding. In this work, we have applied computational approach to unravel the differentially expressed genes, their networks for the enriched pathways. Based on our results, we conclude that among the most dominantly altered pathways for renal cell carcinoma, are PI3K-Akt, Foxo, endocytosis, MAPK, Tight junction, cytokine-cytokine receptor interaction pathways and the major source of alteration for these pathways are MAP3K13, CHAF1A, FDX1, ARHGAP26, ITGBL1, C10orf118, MTO1, LAMP2, STAMBP, DLC1, NSMAF, YY1, TPGS2, SCARB2, PRSS23, SYNJ1, CNPPD1, PPP2R5E. In terms of clinical significance, there are large number of differentially expressed genes which appears to be playing critical roles in survival.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Biologia Computacional , Procedimentos Clínicos , Feminino , Proteínas Ativadoras de GTPase/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Integrina beta1 , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Fosfatase 2/metabolismo , Proteínas Supressoras de Tumor/genética
9.
Mol Med ; 28(1): 47, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508972

RESUMO

BACKGROUND: Receptor-interacting protein kinase 2 (RIPK2, also known as RIP2) was reported to be associated with bacterial infections as well as inflammatory responses. However, the role of RIPK2 in prognosis and immunotherapy response is yet to be elucidated in human pan-cancer. METHODS: In this study, we investigated the expression, gene alteration landscape and prognostic value of RIPK2 in 33 cancers through various databases including Ualcan, cBioportal and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Then, the correlation between RIPK2 and immune infiltration, immune score, stromal score, and ESTIMATE score was investigated in the Cancer Genome Atlas (TCGA) and tumor immune estimation resource (TIMER) databases. Independent cohorts were utilized to explore the role of RIPK2 in tumor immunotherapy response. Furthermore, Gene set enrichment analysis (GSEA) was conducted to explore the mechanisms by which RIPK2 regulates immune therapy resistance. Single-cell RNA-seq datasets were used to analyze the expression level of RIPK2 on different immune cells. Moreover, CellMiner database was used to explore the relationship between RIPK2 expression with drug response. RESULT: Compared with normal tissue, tumor tissue had a higher expression level of RIPK2 in various cancers. Survival analysis showed that high expression of RIPK2 associated with poor prognosis in numerous cancers. RIPK2 was found to promote a series of immune cell infiltration and B cells, macrophages, and neutrophils were significantly positively correlated with the expression of RIPK2. Moreover, RIPK2 affected immune score, stromal score and ESTIMATE score for a wide range of cancers. In the vast majority of 33 cancers, gene co-expression analysis showed that RIPK2 was positively correlated with the expression of immune checkpoint markers, such as PDCD1 (PD-1), CD274 (PD-L1), CTLA4 and TIGIT. RIPK2 aggravated cytotoxic T lymphocyte (CTL) dysfunction and related to the poor efficacy of immune checkpoint blockade in skin cutaneous melanoma (SKCM) and kidney renal clear cell carcinoma (KIRC). High expression of RIPK2 promoted innate immunotherapy resistance and adaptive immunotherapy resistance through IL-6/JAK/STAT3 signaling, interferon-gamma response, and interferon-alpha response pathway. CONCLUSIONS: These results confirmed that RIPK2 could serve as a prognostic biomarker and promoted immune therapy resistance via triggering cytotoxic T lymphocytes dysfunction.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Melanoma , Neoplasias Cutâneas , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Citotóxicos/patologia
10.
STAR Protoc ; 3(2): 101306, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35496785

RESUMO

We developed an in vivo serial passaging model for renal cancer with orthotopic renal subcapsular inoculation. We detail the procedures for renal subcapsular inoculation of cancer cells in mice, followed by in vivo and ex vivo bioluminescence imaging, tumor-bearing kidney dissociation, and in vivo passaging. This protocol is capable of reproducing the coevolution between cancer cells and the primary tumor microenvironment. It enables us to unveil the systemic dynamics of metastasis and develop a therapeutic strategy for metastatic renal cancer. For complete details on the use and execution of this protocol, please refer to Nishida et al. (2020).


Assuntos
Neoplasias Renais , Transplantes , Animais , Diagnóstico por Imagem , Feminino , Humanos , Rim/patologia , Neoplasias Renais/patologia , Masculino , Camundongos , Transplantes/patologia , Microambiente Tumoral
11.
Acta Med Okayama ; 76(2): 155-165, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35503443

RESUMO

Small bowel metastasis from renal cell carcinoma (RCC) is rare, and its clinicopathological characteristics are unclear; thus, we revisited the concept of this tumor and reviewed its diagnostic and treatment modalities. We filtered MEDLINE searches of articles published in English between 1950 and 2019, and identified 100 patients who had undergone treatment, including 1 patient from our clinic. We extracted patient characteristics, treatment, and prognostic data, resulting in clinicopathological data on 100 patients (83 men, 17 women). Mean age was 63 years (range, 16-86 years). Tumor sites were duodenum, jejunum, ileum, and multiple sites in 30, 37, 25, and 7 patients, respectively. The 1-, 3-, and 5-year overall survival rates after diagnosis were 53.0%, 36.0%, and 36.0%. Curative resection patients showed 62.1% 5-year survival after surgery, vs. 27.5% in noncurative surgical management cases. Good prognoses can be expected if these tumors are identified early for complete removal. Surgery is the only curative option. To determine the best management strategy and improve prognostic accuracy, we continue to collect and analyze epidemiological and pathological data. Although this condition is rare, surgery should be considered if curative resection is expected. Prognosis after curative resection is not poor, but recurrence is not unlikely.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
12.
Acta Med Okayama ; 76(2): 225-228, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35503451

RESUMO

A 75-year-old man presented to our hospital 1 year after partial renal resection for clear cell carcinoma. A right lower lobe lung nodule noted at the time of surgery had increased to 3.0 cm in diameter and was confirmed as squamous cell lung carcinoma by bronchoscopic cytology. Computed tomography had also revealed paratracheal lymph node swelling. He underwent right lower lobectomy with lymph node dissection by video-assisted thoracic surgery. Pathological examination confirmed squamous cell carcinoma of the lung but diagnosed the right hilar and mediastinal lymph node metastases as clear cell carcinoma.


Assuntos
Carcinoma de Células Renais , Carcinoma de Células Escamosas , Neoplasias Renais , Neoplasias Pulmonares , Idoso , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Pulmão/patologia , Neoplasias Pulmonares/patologia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Estadiamento de Neoplasias
13.
Anal Cell Pathol (Amst) ; 2022: 2721005, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509814

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common histological and devastating subtype of renal cell carcinoma. Necroptosis is a form of programmed cell death that causes prominent inflammatory responses. miRNAs play a significant role in cancer progression through necroptosis. However, the prognostic value of necroptosis-related miRNAs remains ambiguous. In this study, 39 necroptosis-related miRNAs (NRMs) were extracted and 17 differentially expressed NRMs between normal and tumor samples were identified using data form The Cancer Genome Atlas (TCGA). After applying univariate Cox proportional hazard regression analysis and LASSO Cox regression model, six necroptosis-related miRNA signatures were identified in the training cohort and their expression levels were verified by qRT-PCR. Using the expression levels of these miRNAs, all patients were divided into the high- and low-risk groups. Patients in the high-risk group showed poor overall survival (P < 0.0001). Time-dependent ROC curves confirmed the good performance of our signature. The results were verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression models demonstrated that the risk score was an independent prognostic factor. Additionally, a predictive nomogram with good performance was constructed to enhance the implementation of the constructed signature in a clinical setting. We then employed miRBD, miRTarBase, and TargetScan to predict the target genes of six necroptosis-related miRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that 392 potential target genes were enriched in cell proliferation-related biological processes. Six miRNAs and 59 differentially expressed target genes were used to construct an miRNA-mRNA interaction network, and 11 hub genes were selected for survival and tumor infiltration analysis. Drug sensitivity analysis revealed potential drugs that may contribute to cancer management. Hence, necroptosis-related genes play an important role in cancer biology. We developed, for the first time, a necroptosis-related miRNA signature to predict ccRCC prognosis.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Necroptose/genética
14.
BMC Nephrol ; 23(1): 172, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513791

RESUMO

BACKGROUND: The dysfunction of RNA binding proteins (RBPs) is associated with various inflammation and cancer. The occurrence and progression of tumors are closely related to the abnormal expression of RBPs. There are few studies on RBPs in clear cell renal carcinoma (ccRCC), which allows us to explore the role of RBPs in ccRCC. METHODS: We obtained the gene expression data and clinical data of ccRCC from the Cancer Genome Atlas (TCGA) database and extracted all the information of RBPs. We performed differential expression analysis of RBPs. Risk model were constructed based on the differentially expressed RBPs (DERBPs). The expression levels of model markers were examined by reverse transcription-quantitative PCR (RT-qPCR) and analyzed for model-clinical relevance. Finally, we mapped the model's nomograms to predict the 1, 3 and 5-year survival rates for ccRCC patients. RESULTS: The results showed that the five-year survival rate for the high-risk group was 40.2% (95% CI = 0.313 ~ 0.518), while the five-year survival rate for the low-risk group was 84.3% (95% CI = 0.767 ~ 0.926). The ROC curves (AUC = 0.748) also showed that our model had stable predictive power. Further RT-qPCR results were in accordance with our analysis (p < 0.05). The results of the independent prognostic analysis showed that the model could be an independent prognostic factor for ccRCC. The results of the correlation analysis also demonstrated the good predictive ability of the model. CONCLUSION: In summary, the 4-RBPs (EZH2, RPL22L1, RNASE2, U2AF1L4) risk model could be used as a prognostic indicator of ccRCC. Our study provides a possibility for predicting the survival of ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Prognóstico , Proteínas de Ligação a RNA/genética
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(3): 328-333, 2022 Mar 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35545325

RESUMO

OBJECTIVES: Renal cancer is a common malignancy of the urinary system, and the partial nephrectomy is a common surgical modality for early renal cancer. 3D printing technology can create a visual three-dimensional model by using 3D digital models of the patient's imaging data. With this model, surgeons can perform preoperative assessment to clarify the location, depth, and blood supply of the tumor, which helps to develop preoperative plans and achieve better surgical outcomes. In this study, the R.E.N.A.L scoring system was used to stratify patients with renal tumors and to explore the clinical application value of 3D printing technology in laparoscopic partial nephrectomy. METHODS: A total of 114 renal cancer patients who received laparoscopic partial nephrectomy in Xiangya Hospital from June 2019 to December 2020 were enrolled. The patients were assigned into an experimental group (n=52) and a control group (n=62) according to whether 3D printing technology was performed, and the differences in perioperative parameters between the 2 groups were compared. Thirty-nine patients were assigned into a low-complexity group (4-6 points), 32 into a moderate-complexity group (7-9 points), and 43 into a high-complexity group (10-12 points) according to R.E.N.A.L score, and the differences in perioperative parameters between the experimental group and the control group in each score group were compared. RESULTS: The experimental group had shorter operative time, renal ischemia time, and postoperative hospital stay (all P<0.05), less intraoperative blood loss (P=0.047), and smaller postoperative blood creatinine change (P=0.032) compared with the control group. In the low-complexity group, there were no statistically significant differences between the experimental group and the control group in operation time, renal ischemia time, intraoperative blood loss, postoperative blood creatinine changes, and postoperative hospital stay (all P>0.05). In the moderate- and high- complexity groups, the experimental group had shorter operative time, renal ischemia time, and postoperative hospital stay (P<0.05 or P<0.001), less intraoperative blood loss (P=0.022 and P<0.001, respectively), and smaller postoperative blood creatinine changes (P<0.05 and P<0.001, respectively) compared with the control group. CONCLUSIONS: Compared with renal tumor patients with R.E.N.A.L score<7, renal cancer patients with R.E.N.A.L score≥7 may benefit more from 3D printing assessment before undergoing partial nephrectomy.


Assuntos
Neoplasias Renais , Laparoscopia , Perda Sanguínea Cirúrgica , Creatinina , Feminino , Humanos , Isquemia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Masculino , Nefrectomia/métodos , Impressão Tridimensional , Estudos Retrospectivos , Resultado do Tratamento
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(4): 473-485, 2022 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-35527483

RESUMO

OBJECTIVE: To conduct a pan-cancer analysis of the expression of long non-coding RNA (lncRNA) MIR22HG and explore its association with clinical characteristics. METHODS: We analyzed the expression of MIR22HG in different tumors and its association with clinical staging, lymph node metastasis, tumor mutation burden (TMB) and microsatellite instability (MSI) using R package based on the Cancer Genome Atlas (TCGA) datasets. The relationship between MIR22HG expression and infiltrating immune cells was analyzed using TIMER algorithm. The association of MIR22HG gene alteration frequency with the clinical outcomes was examined using cBioPortal online software. Data form Genomics of Drug Sensitivity in Cancer (GDSC) were used to analyze the relationship between MIR22HG and the sensitivity of chemotherapy drugs. We specifically analyzed MIR22HG expression in hepatocellular carcinoma (HCC) and its correlation with sorafenib treatment using GEO database and verified the results in 12 pairs of HCC specimens. Kaplan-Meier analysis was performed to analyze the correlation of MIR22HG with the outcomes of sorafenib treatment. We also tested the effects of MIR22HG overexpression and knockdown on IC50 of sorafenib in HCC cells. RESULTS: MIR22HG was downregulated in most tumors (P < 0.05), where its deletion mutations were frequent, and associated with a poor prognosis (P < 0.05). In many tumors, MIR22HG expression level was correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, immune checkpoint-related genes, and sensitivity to common chemotherapeutic drugs (P < 0.05). Among the 6 common infiltrating immune cells in cancers, neutrophil infiltration had the strongest correlation with MIR22HG expression level, especially in breast cancer, rectal cancer and kidney renal papillary cell carcinoma (P < 0.05). MIR22HG was downregulated in HCC in association with HCC progression (P < 0.05). In HCC patients, a low MIR22HG expression was associated with a favorable outcome after sorafenib treatment (HR=2.94, P=0.075) and was capable of predicting the response to sorafenib treatment (AUC=0.8095). Compared with the negative control, MIR22HG overexpression obviously reduced sorafenib sensitivity (with IC50 of 7.731 vs 15.61) while MIR22HG knockdown increased sorafenib sensitivity of HCC cells (with IC50 of 7.986 vs 5.085). CONCLUSION: MIR22HG expression level is correlated with clinical stage, lymph node metastasis, TMB, MSI, immune cell infiltration, and chemosensitivity in most cancer, suggesting its potential as an immunotherapeutic target and also a prognostic biomarker for tumors.


Assuntos
Carcinoma Hepatocelular , Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Hepáticas , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Hepáticas/patologia , Metástase Linfática , Masculino , Instabilidade de Microssatélites , RNA Longo não Codificante/genética , Sorafenibe/farmacologia
17.
Comput Math Methods Med ; 2022: 8504441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529267

RESUMO

Clear cell renal carcinoma (ccRCC) is one of the most common renal carcinomas worldwide, which has worse prognosis compared with other subtypes of tumors. We propose a potential RNA regulatory mechanism associated with ccRCC progression. Accordingly, we screened out clinical factors and the expression of RNAs and miRNAs of ccRCC from the TCGA database. 9 lncRNAs (FGF12-AS2, WT1-AS, TRIM36-IT1, AC009093.1, LINC00443, TCL6, COL18A1-AS1, AC110619.1, HOTTIP), 2 miRNAs (mir-155 and mir-21), and 3 mRNAs (COL4A4, ERMP1, PRELID2) were selected from differential expression RNAs and built predictive survival models. The survival models performed very well in predicting prognosis and were found to be highly correlated with tumor stage. In addition, the survival-related lncRNA-miRNA-mRNA (ceRNA) network was constructed by 18 RNAs including 12 mRNAs, 2 miRNAs, and 4 lncRNAs. It is found that the "ECM-receptor interaction," "Pathways in cancer," and "Chemokine signaling pathway" as the main pathways in KEGG pathway analysis. Overall, we established predictive survival model and ceRNA network based on multivariate Cox regression analysis. It may open a new approach and potential biomarkers for clinical prognosis and treatment of ccRCC patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Feminino , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/genética , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
18.
JCI Insight ; 7(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35531954

RESUMO

MicroRNAs (miRNAs) belong to a class of endogenous small noncoding RNAs that regulate gene expression at the posttranscriptional level, through both translational repression and mRNA destabilization. They are key regulators of kidney morphogenesis, modulating diverse biological processes in different renal cell lineages. Dysregulation of miRNA expression disrupts early kidney development and has been implicated in the pathogenesis of developmental kidney diseases. In this Review, we summarize current knowledge of miRNA biogenesis and function and discuss in detail the role of miRNAs in kidney morphogenesis and developmental kidney diseases, including congenital anomalies of the kidney and urinary tract and Wilms tumor. We conclude by discussing the utility of miRNAs as potentially novel biomarkers and therapeutic agents.


Assuntos
Neoplasias Renais , MicroRNAs , Tumor de Wilms , Feminino , Regulação da Expressão Gênica , Humanos , Rim/metabolismo , Neoplasias Renais/metabolismo , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Tumor de Wilms/genética
19.
Cell Death Dis ; 13(5): 443, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525866

RESUMO

Metabolic dysfunction is seen in cancer cells where increased glycolysis provides energy for growth. Circular RNAs (circRNAs) are thought to assist in glucose metabolism and the switch to glycolysis. Through screening, we found that circVAMP3 was necessary for both glycolytic and proliferative activities in renal cell carcinoma (RCC). Furthermore, circVAMP3 expression was elevated in RCC patients in correspondence with TNM stage. Mechanistically, circVAMP3 was observed to interact directly with lactate dehydrogenase A (LDHA) and modulate its activity. The circVAMP3-LDHA interaction facilitated LDHA phosphorylation at tyrosine 10 (Y10) catalyzed by the upstream kinase fibroblast growth factor receptor type 1 (FGFR1). Therefore, this study reveals a novel molecular mechanism by which circVAMP3 promotes glycolysis and proliferation through regulating the enzymatic activity of glycolytic enzyme, suggesting that circVAMP3 may represent an RCC biomarker and treatment target.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glicólise/genética , Humanos , Neoplasias Renais/genética , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5 , Masculino , RNA Circular/genética
20.
Arch Esp Urol ; 75(3): 248-255, 2022 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-35435169

RESUMO

INTRODUCTION: The increased incidenceof diagnosis of kidney tumours has driveninvestigation in the area. It is known that the risk ofmalignancy is correlated with tumour size, but thereare still no specific and objective parameters to characterizethe degree of aggressiveness and to be ableto guide a treatment reliably. OBJECTIVE: To identify the relationship betweenrenal tumour size and the incidence of tumour aggressivecharacteristics. PATIENTS AND METHODS: A retrospective analysisof our series of renal cancers operated between 1998and 2018 was performed. The specific and cumulativeincidence of aggressive characteristics was studied.The following where considered as aggressive characteristics:Presence of sarcomatoid or epidermoiddifferentiation, tumour necrosis, stage pT3-4, histologicalhigh grade (3-4) and the presence of histologicalaggressive variants. RESULTS: A total of 651 patients that had undergonerenal mass surgery were analysed. In tumours below2 cm the appearance of aggressive characteristicsoccurred in less than 5%. For renal masses greaterthan 2 cm, each centimetre increase correlated with arise in cumulative incidence of 2-3% for each characteristicstudied. CONCLUSIONS: In tumours below 2cm and patientswith significant comorbidities active surveillance maybe a reliable alternative to surgery.


INTRODUCCIÓN: El aumento de incidenciade diagnóstico de tumores renales ha conllevadoun mayor estudio y conocimiento de los mismos.Se conoce que el riesgo de malignidad se correlacionacon el tamaño tumoral, pero seguimos sin tener parámetrosespecíficos y objetivos para caracterizar elgrado de agresividad de los mismos y poder orientarun tratamiento de forma fiable. OBJETIVO: Identificar la relación que existe entre eltamaño tumoral y la incidencia de características deagresividad.MATERIAL Y MÉTODOS: Análisis retrospectivo denuestra serie de cáncer renal intervenido quirúrgicamenteen el periodo entre 1998 y 2018. Se estudia laincidencia específica y acumulada de las característicasde agresividad en dichas lesiones y su relación conel tamaño tumoral. Se consideraron característicasde agresividad: la presencia diferenciación sarcomatoiode epidermoide, necrosis tumoral, estadio pT3-4,grado histológico alto (3-4) y la presencia de variantesde histología agresiva. RESULTADOS: Se analizan un total de 651 pacientesintervenidos por cáncer renal. En tumores por debajode 2 cm la aparición de características de agresividadse observó en menos del 5%. A partir de ese tamaño, laincidencia acumulada se incrementa en un 2-3% paracada característica con cada centímetro que aumentael tamaño tumoral. CONCLUSIONES: Este análisis demuestra que conformeaumenta el tamaño de los tumores renales, aumentala incidencia de características de agresividadde los mismos. En tumores por debajo de 2 cm y pacientescon comorbilidades importantes la vigilanciaactiva puede ser una alternativa con cierta seguridad.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Rim/patologia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Nefrectomia , Estudos Retrospectivos
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