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OBJECTIVES: To determine the integrative value of contrast-enhanced computed tomography (CECT), transcriptomics data and clinicopathological data for predicting the survival of bladder urothelial carcinoma (BLCA) patients. METHODS: RNA sequencing data, radiomics features and clinical parameters of 62 BLCA patients were included in the study. Then, prognostic signatures based on radiomics features and gene expression profile were constructed by using least absolute shrinkage and selection operator (LASSO) Cox analysis. A multi-omics nomogram was developed by integrating radiomics, transcriptomics and clinicopathological data. More importantly, radiomics risk score-related genes were identified via weighted correlation network analysis and submitted to functional enrichment analysis. RESULTS: The radiomics and transcriptomics signatures significantly stratified BLCA patients into high- and low-risk groups in terms of the progression-free interval (PFI). The two risk models remained independent prognostic factors in multivariate analyses after adjusting for clinical parameters. A nomogram was developed and showed an excellent predictive ability for the PFI in BLCA patients. Functional enrichment analysis suggested that the radiomics signature we developed could reflect the angiogenesis status of BLCA patients. CONCLUSIONS: The integrative nomogram incorporated CECT radiomics, transcriptomics and clinical features improved the PFI prediction in BLCA patients and is a feasible and practical reference for oncological precision medicine. KEY POINTS: ⢠Our radiomics and transcriptomics models are proved robust for survival prediction in bladder urothelial carcinoma patients. ⢠A multi-omics nomogram model which integrates radiomics, transcriptomics and clinical features for prediction of progression-free interval in bladder urothelial carcinoma is established. ⢠Molecular functional enrichment analysis is used to reveal the potential molecular function of radiomics signature.
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Nomogramas , Tomografia Computadorizada por Raios X/métodos , Transcriptoma/genética , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/genética , Adulto , Meios de Contraste , Feminino , Humanos , Masculino , Prognóstico , Intensificação de Imagem Radiográfica/métodos , Fatores de Risco , Análise de Sobrevida , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND Bladder carcinoma (BLCA) is a leading cause of cancer-related deaths worldwide. The aim of this work was to develop an accurate stratification in predicting the prognosis and directing the treatment of BLCA patients based on small nucleolar RNAs (snoRNAs). MATERIAL AND METHODS Expression profiles of snoRNAs were downloaded from the SNORic database. The expression profiles and clinical outcomes of BLCA patients were analyzed. Survival-associated snoRNAs were identified and used to develop a novel risk score classifier. Genes in the whole genome that were significantly correlated with the included prognostic snoRNAs were used for functional enrichment analysis. RESULTS The results showed that age, American Joint Committee on Cancer (AJCC) stage, and tumor status were significantly correlated with overall survival (OS) of BLCA patients. We selected 12 survival-associated snoRNAs to build a prognostic signature. Patients were separated into high- and low-risk groups based on the median value of the risk score. Patients in the high-risk group and low-risk group have distinct clinical outcomes. The AJCC TNM stage showed moderate utility as a prognostic indicator for clinical outcome prediction. Then, clinical parameters and risk scores were entered in multivariate Cox analysis. Notably, the prognostic signature remained an independent significant prognostic risk factor. The pathway analysis suggested that these genes were enriched in several types of cancer and "Focal adhesion" pathways. CONCLUSIONS The prognostic signature defined by expression profiles of 12 survival-associated snoRNAs appears to be an excellent predictor of the clinical outcome of BLCA patients.
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Carcinoma/diagnóstico , RNA Nucleolar Pequeno/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma/epidemiologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/epidemiologiaRESUMO
BACKGROUND microRNAs (miRNAs) have a role as biomarkers in human cancer. The aim of this study was to use bioinformatics data, and review of cases identified from the literature, to investigate the role of microRNA-99a-3p (miR-99a-3p) in prostate cancer, including the identification of its target genes and signaling pathways. MATERIAL AND METHODS Meta-analysis from a literature review included 965 cases of prostate cancer. Bioinformatics databases interrogated for miR-99a-3p in prostate cancer included The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and ArrayExpress. Twelve computational predictive algorithms were developed to integrate miR-99a-3p target gene prediction data. Bioinformatics analysis data from Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analysis were used investigate the possible pathways and target genes for miR-99a-3p in prostate cancer. RESULTS TCGA data showed that miR-99a was down-regulated in prostate cancer when compared with normal prostate tissue. Receiver-operating characteristic (ROC) curve area under the curve (AUC) for miR-99a-3p was 0.660 (95% CI, 0.587-0.732) or a moderate level of discriminations. Pathway analysis showed that miR-99a-3p was associated with the Wnt and vascular endothelial growth factor (VEGF) signaling pathways. The PPP3CA and HYOU1 genes, selected from the PPI network, were highly expressed in prostate cancer tissue compared with normal prostate tissue, and negatively correlated with the expression of miR-99a-3p. CONCLUSIONS In prostate cancer, miR-99a-3p expression was associated with the Wnt and VEGF signaling pathways, which might inhibit the expression of PPP3CA or HYOU1.
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Biologia Computacional , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Próstata/genética , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Genoma Humano , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Mapas de Interação de Proteínas/genética , Reprodutibilidade dos TestesRESUMO
A new metal-formate framework, poly[1H-imidazol-3-ium [tri-µ2-formato-manganese(II)]], {(C3H5N2)[Mn(HCOO)3]}n, was synthesized and its structural phase transition was studied by thermal analysis and variable-temperature X-ray diffraction analysis. The transition temperature is around 435â K. The high-temperature phase is tetragonal and the low-temperature phase is monoclinic, with a ß angle close to 90°. The relationship of the unit cells between the two phases can be described as: a(HT) = 0.5a(LT) + 0.5b(LT); b(HT) = -0.5a(LT) + 0.5b(LT); c(HT) = 0.5c(LT). In the high-temperature phase, both the framework and the guest 1H-imidazol-3-ium (HIm) cations are disordered; the HIm cations are located about 2mm sites and were modelled as fourfold disordered. The Mn and a formate C atom are located on fourfold rotary inversion axes, while another formate C atom is on a mirror plane. The low-temperature structure is ordered and consists of two crystallographically independent HIm cations and two crystallographically independent Mn(2+) ions. The phase transition is attributable to the order-disorder transition of the HIm cations.
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Background: Bladder cancer (BLCA) is a malignant tumor occurring in bladder mucosa. Metadherin (MTDH) has been implicated in tumor progression; however, its molecular biological mechanisms in BLCA remain unclear. Materials and Methods: Cell functions were tested after BLCA cells were transfected by both short hairpin RNAs and small interfering RNAs to silence MTDH. Furthermore, in-house RNA sequencing (RNA-seq) was performed with T24 cells after the knockdown of MTDH. In addition, MTDH-related pathways were explored. Finally, MTDH mRNA and protein expression levels were examined using multiple detection methods in BLCA tissues. Results: MTDH knockdown could largely inhibit cell proliferation, viability, and migration and induce apoptosis of BLCA cells. In-house RNA-seq showed that MTDH knockdown led to extracellular matrix organization and cell division. The integrated analysis showed that the comprehensive expression of MTDH at the mRNA level was 0.47 and that at the protein level was 0.54, based on 11 platforms, including 1485 BLCA and 180 non-BLCA samples. Conclusions: MTDH promotes the growth of BLCA cells through the pathway of cell division. This study provides new directions and biomarkers for future treatment.
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Neoplasias da Bexiga Urinária , Humanos , RNA Interferente Pequeno/genética , Neoplasias da Bexiga Urinária/genética , Divisão Celular , Proliferação de Células , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
Bladder cancer (BC) is a common cancer worldwide with a high prevalence. This study was conducted to elucidate the expression and clinical significance of Sorbin and SH3 domain-containing protein 1 (SORBS1) in BC as well as to explore its molecular mechanism in BC tumourigenesis. RNA-sequencing data, microarray, and Immunohistochemistry (IHC) were applied to elucidated the SORBS1 expression at multiple levels. After that, the relationship between tumour-immune infiltration and SORBS1 was also explored. Finally, SORBS1-related genes in BC were identified to perform functional enrichment analyses. The expression integration revealed that the comprehensive expression of SORBS1 at the mRNA level was -1.02 and that at the protein level was -3.73, based on 12 platforms, including 1221 BC and 187 non-BC samples. SORBS1 was negatively correlated with tumour purity (correlation = -0.342, p < 0.001) and positively correlated with macrophage (correlation = 0.358, p < 0.001). The results of enrichment analyses revealed that the most significant biological pathways of SORBS1-related genes were epithelial-mesenchymal transition. SORBS1 was significantly down-regulated in BC and may play a role as tumour suppressor. This study provides new directions and biomarkers for future BC diagnosis.
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Relevância Clínica , Neoplasias da Bexiga Urinária , Humanos , Regulação para Baixo , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Neoplasias da Bexiga Urinária/genética , Regulação Neoplásica da Expressão GênicaRESUMO
The title double mol-ecular salt, (C(6)H(14)N(2))[Cd(H(2)O)(6)](SO(4))(2), is an isostructure of its Mn and Co analogues. The Cd(II) atom adopts a near-regular CdO(6) octa-hedral coordination geometry. The crystal structure can be described as an alternation of cationic and anionic layers along [010], and numerous O-Hâ¯O and N-Hâ¯O hydrogen bonds are observed. No thermal anomalies corresponding to possible phase transitions were observed in DSC (differential scanning calorimetry) measurements and the 93â K structure is almost the same as the room-temperature structure.
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Bladder cancer (BC) ranks as the ninth most commonly diagnosed cancer worldwide. The presence of a transcription factor (TF) has been uncovered as a significant contributor to the pathophysiological changes of cancers. In present study, we elucidated the expression and clinical significance of Homeobox A11 (HOXA11) in BC for the first time, and originally investigated HOXA11 as a TF. Employing in-house immunohistochemistry (IHC), we incorporated 137 BC and 34 non-BC cases to detect the expression of HOXA11 protein in BC tissues. HOXA11-related RNA-sequencing (RNA-seq) expression and RNA microarrays were collected from public databases, the "sva" and "limma" R packages were implemented to integrate and normalize the RNA-seq data and microarrays separately. Integration expression was carried out to further evaluate the HOXA11 expression by utilizing the standard mean difference (SMD). The expression level of HOXA11 in various BC cell lines was also evaluated. We further systematically analyzed the downstream target genes of HOXA11 in BC by utilizing Chromatin Immunoprecipitation Sequencing (ChIP-seq) profiles, differentially expressed genes (DEGs), and HOXA11-related genes. Modification of histone marks on the promoter region of target genes were also discovered by histone ChIP-seq data. Results of the IHC and RNA-seq revealed the protein and mRNA expression of HOXA11 was significantly decreased in BC tissues compared to non-BC tissues (2.98 ± 1.48 vs. 8.23 ± 2.64; 6.87 ± 1.54 vs. 8.38 ± 1.42). Five platforms significantly revealed the down-regulation of HOXA11 expression in BC (GPL96, GPL570, GPL6102, GPL6884, and GPL13497). A similar decreased trend was discovered in BC tissues in expression integration with the incorporated SMD reaching -0.843 (-1.362 ~ -0.325, p = 0.001) and -1.051 (-1.674 ~ -0.428, p = 0.001). Expression of HOXA11 was down-regulated in most of the BC cell lines. COL1A1 was considered as a final HOXA11 target gene and positively related to HOXA11 with the correlation coefficient as 0.584 (95% CI: 0.371-0.739, p < 0.001). HOXA11 regulates COL1A1 expression in BC via H3K27ac modification. The expression of COL1A1 was down-regulated with the SMD reached -0.312 (p < 0.001). In conclusion, HOXA11 expression is markedly decreased and might promote the transcription of COL1A1 to inhibit BC.
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Genes Homeobox , Neoplasias da Bexiga Urinária , Regulação da Expressão Gênica , Proteínas de Homeodomínio , Humanos , RNA , Fatores de Transcrição/genética , Neoplasias da Bexiga Urinária/genéticaRESUMO
BACKGROUND: The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. MATERIALS AND METHODS: The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. RESULTS: The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. CONCLUSION: miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.
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Neoplasias Ósseas/secundário , Carcinogênese/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteína Quinase CDC2/metabolismo , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/diagnóstico , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Curva ROC , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Tumor-infiltrating immune cells are indispensable to the progression and prognosis of clear cell renal cell carcinoma (ccRCC). OBJECTIVE: The aim of this study was to explore the clinical implications of immune cell infiltrates in ccRCC. METHODS: The Cancer Genome Atlas (TCGA) database (N= 515) and E-MTAB-1980 cohort of patients (N= 101) were adopted to estimate the prognostic value of immune cell infiltration. Twenty-four types of immune cells were evaluated using single-sample gene set enrichment analysis. Cox regression analyses were conducted to develop an immune risk score. RESULTS: Survival analyses revealed that 13 genes significantly associated with the overall survival (OS). Furthermore, multivariate Cox analysis identified an immune risk score on the basis of mast cells, natural killer CD56bright cells, T helper 17 (Th17) cells, and Th2 cells. The immune risk score was associated with OS, with hazard ratios of 2.72 (95% CI 2.17-3.40) and 3.24 (95% CI 1.64-6.44) in TCGA and E-MTAB-1980 datasets, respectively. This immune risk score was significantly correlated with some immunotherapy-related biomarkers. CONCLUSIONS: We profiled a prognostic signature and established an immune risk score model for ccRCC, which could provide novel predictive markers for patients with ccRCC and an indicator for immunotherapy response measurement.
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Carcinoma de Células Renais/imunologia , Neoplasias Renais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/genética , Neoplasias Renais/patologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Neoplásico/genética , RNA Neoplásico/imunologia , Taxa de SobrevidaRESUMO
Alternative splicing (AS) is a major mechanism that greatly enhanced the diversity of proteome. Mounting evidence demonstrated that aberration of AS are important steps for the initiation and progression of human cancers. Here, we comprehensively investigated the association between whole landscape of AS profiles and the survival outcome of renal cell carcinoma (RCC) patients using RNA-seq data from TCGA SpliceSeq. Because of the limited number size of deaths in kidney chromophobe renal cell carcinoma (KICH) and papillary renal cell carcinoma (KIRP) TCGA cohorts, we only conducted survival analysis in kidney clear renal cell carcinoma (KIRC). We further constructed prognostic index (PI) based on prognosis-related AS events and built correlation network for splicing factors and prognosis-related AS events. According to the results, a total of 5351 AS events in 3522 genes were significantly correlated with the overall survival (OS) of kidney clear cell renal cell carcinoma (KIRC) patients. Seven of the PI models exhibited preferable prognosis-predicting capacity for KIRC with PI-ALL reaching the highest area under curve value of 0.875. The splicing regulatory network between splicing factors and prognosis-related AS events depicted a tangled web of relationships between them. One of the splicing factors: KHDRBS3 was validated by immunohistochemistry to be down-regulated in KIRC tissues. In conclusion, the powerful efficiency of risk stratification of PI models indicated the potential of AS signature as promising prognostic markers for KIRC and the splicing regulation network provided possible genetic mechanism of KIRC.
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Papillary renal cell carcinoma (PRCC) accounts for 1520% of all kidney neoplasms and continually attracts attention due to the increase in the incidents in which it occurs. The molecular mechanism of PRCC remains unclear and the efficacy of drugs that treat PRCC lacks sufficient evidence in clinical trials. Therefore, it is necessary to investigate the underlying mechanism in the development of PRCC and identify additional potential antiPRCC drugs for its treatment. The differently expressed genes (DEGs) of PRCC were identified, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses for functional annotation. Then, potential drugs for PRCC treatment were predicted by Connectivity Map (Cmap) based on DEGs. Furthermore, the latent function of query drugs in PRCC was explored by integrating drugtarget, drugpathway and drugprotein interactions. In total, 627 genes were screened as DEGs, and these DEGs were annotated using KEGG pathway analyses and were clearly associated with the complement and coagulation cascades, amongst others. Then, 60 candidate drugs, as predicted based on DEGs, were obtained from the Cmap database. Vorinostat was considered as the most promising drug for detailed discussion. Following proteinprotein interaction (PPI) analysis and molecular docking, vorinostat was observed to interact with C3 and ANXN1 proteins, which are the upregulated hub genes and may serve as oncologic therapeutic targets in PRCC. Among the top 20 metabolic pathways, several significant pathways, such as complement and coagulation cascades and cell adhesion molecules, may greatly contribute to the development and progression of PRCC. Following the performance of the PPI network and molecular docking tests, vorinostat exhibited a considerable and promising application in PRCC treatment by targeting C3 and ANXN1.
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Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Renais/genética , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/química , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Biologia Computacional , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/genética , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular/métodos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , Vorinostat/química , Vorinostat/farmacologia , Vorinostat/uso terapêuticoRESUMO
Purpose: Autophagy is a major catabolic system by which eukaryotic cells undergo self-degradation of damaged, defective, or unwanted intracellular components. An abnormal autophagic level is implicated in the pathogenesis of multiple diseases, including cancers. The aim of this study is to explore the prognostic value of autophagy in bladder cancer (BC), which is a major cause of cancer-related death globally. Patients and methods: First, 27 differentially expressed autophagy-related genes (ARGs) were identified in BC patients based on The Cancer Genome Atlas (TCGA) database. Functional enrichment analyses hinted that autophagy may act in a tumor-suppressive role in the initiation of BC. Then, the Cox proportional hazard regression model were employed to identify three key prognostic ARGs (JUN, MYC, and ITGA3), which were related with overall survival (OS) significantly in BC. The three genes represented important clinical significance and prognostic value in BC. Then a prognostic index (PI) was constructed. Results: The PI was constructed based on the three genes, and significantly stratified BC patients into high- and low-risk groups in terms of OS (HR=1.610, 95% CI=1.200-2.160, P=0.002). PI remained as an independent prognostic factor in multivariate analyses (HR=2.355, 95% CI=1.483-3.739, P<0.001). When integrated with clinical characteristics of age and stage, an autophagy-clinical prognostic index (ACPI) was finally validated, which had improved performance in predicting OS of BC patients (HR=2.669, 95% CI=1.986-3.587, P<0.001). The ACPI was confirmed in datasets of GSE13507 (HR=7.389, 95% CI=3.645-14.980, P<0.001) and GSE31684 (HR=1.665, 95% CI=0.872-3.179, P=0.122). Conclusion: This study provides a potential prognostic signature for predicting prognosis of BC patients and molecular insights of autophagy in BC.
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BACKGROUND: Overexpression of metadherin/astrocyte elevated gene-1 (MTDH/AEG-1) has been implicated in various cancers. However, the clinical significance and the potential biological functions of MTDH/AEG-1 in bladder urothelial carcinoma (BUC) are not established. METHODS: In this study, the expression of MTDH/AEG-1in BUC was measured using the Cancer Genome Atlas (TCGA) database and immunohistochemistry, together with a meta-analysis, to investigate the expression and diagnostic value of MTDH/AEG-1. The possible association between MTDH/AEG-1 expression and the viability, proliferation, and apoptosis in BUC cell lines (T24, HT1376, and RT4) was also assessed in vitro by viability, MTS, colony formation, and caspase-3/7 assays, as well as Hoechst 33342 and propidium iodide (PI) double staining. RESULTS: MTDH/AEG-1 expression was significantly higher in BUC tissues than in normal bladder tissues, according to the TCGA and immunohistochemistry results, and these findings were verified by the meta-analysis. Functional knockdown of MTDH/AEG-1 suppressed BUC cell growth and induced apoptosis. Bioinformatics analyses indicated an involvement of MTDH/AEG-1 in several processes, including RNA binding, protein transport, intracellular transport, and the insulin signaling pathway. CONCLUSION: We hypothesize that MTDH/AEG-1 could play essential roles in BUC, especially in cell growth and apoptosis, via the insulin signaling pathway."
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Prostate cancer (PCa) remains a principal issue to be addressed in male cancerassociated mortality. Therefore, the present study aimed to examine the clinical value and associated molecular mechanism of microRNA (miR)1 in PCa. A metaanalysis was conducted to evaluate the diagnosis of miR1 in PCa via Gene Expression Omnibus and ArrayExpress datasets, The Cancer Genome Atlas miR1 expression data and published literature. It was identified that expression of miR1 was significantly downregulated in PCa. Decreased miR1 expression possessed moderate diagnostic value, with area under the curve, sensitivity, specificity and odds ratio values at 0.73, 0.77, 0.57 and 4.60, respectively. Using bioinformatics methods, it was revealed that a number of pathways, including the 'androgen receptor signaling pathway', 'androgen receptor activity', 'transcription factor binding' and 'protein processing in the endoplasmic reticulum', were important in PCa. A total of seven hub genes, including phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS), cadherin 1 (CDH1), SRC protooncogene, nonreceptor tyrosine kinase, twist family bHLH transcription factor 1 (TWIST1), ZW10 interacting kinetochore protein (ZWINT), PCNA clamp associated factor (KIAA0101) and androgen receptor, among which, five (PAICS, CDH1, TWIST1, ZWINT and KIAA0101) were significantly upregulated and negatively correlated with miR1, were identified as key miR1 target genes in PCa. Additionally, it was investigated whether miR1 and its hub genes were associated with clinical features, including age, tumor status, residual tumor, lymph node metastasis, pathological T stage and prostate specific antigen level. Collectively the results suggest that miR1 may be involved in the progression of PCa, and consequently be a promising diagnostic marker. The 'androgen receptor signaling pathway', 'androgen receptor activity', 'transcription factor binding' and 'protein processing in the endoplasmic reticulum' may be crucial interactive pathways in PCa. Furthermore, PAICS, CDH1, TWIST1, ZWINT and KIAA0101 may serve as crucial miR1 target genes in PCa.
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MicroRNAs/genética , Técnicas de Diagnóstico Molecular , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Biologia Computacional/métodos , Bases de Dados de Ácidos Nucleicos , Perfilação da Expressão Gênica , Humanos , Masculino , Metanálise como Assunto , Neoplasias da Próstata/metabolismo , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To investigate the clinical value and potential molecular mechanisms of miR-1 in clear cell renal cell carcinoma (ccRCC). METHODS: We searched the Gene Expression Omnibus (GEO), ArrayExpress, several online publication databases and the Cancer Genome Atlas (TCGA). Continuous variable meta-analysis and diagnostic meta-analysis were conducted, both in Stata 14, to show the expression of miR-1 in ccRCC. Furthermore, we acquired the potential targets of miR-1 from datasets that transfected miR-1 into ccRCC cells, online prediction databases, differentially expressed genes from TCGA and literature. Subsequently bioinformatics analysis based on aforementioned selected target genes was conducted. RESULTS: The combined effect was -0.92 with the 95% confidence interval (CI) of -1.08 to -0.77 based on fixed effect model (I2â¯=â¯81.3%, Pâ¯<â¯0.001). No publication bias was found in our investigation. Sensitivity analysis showed that GSE47582 and 2 TCGA studies might cause heterogeneity. After eliminating them, the combined effect was -0.47 (95%CI: -0.78, -0.16) with I2â¯=â¯18.3%. As for the diagnostic meta-analysis, the combined sensitivity and specificity were 0.90 (95%CI: 0.61, 0.98) and 0.63 (95%CI: 0.39, 0.82). The area under the curve (AUC) in the summarized receiver operating characteristic (SROC) curve was 0.83 (95%CI: 0.80, 0.86). No publication bias was found (Pâ¯=â¯0.15). We finally got 67 genes which were defined the promising target genes of miR-1 in ccRCC. The most three significant KEGG pathways based on the aforementioned genes were Complement and coagulation cascades, ECM-receptor interaction and Focal adhesion. CONCLUSION: The downregulation of miR-1 might play an important role in ccRCC by targeting its target genes.
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Carcinoma Hepatocelular/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Humanos , Prognóstico , Análise Serial de Tecidos/métodosRESUMO
The title salt, C6H6NO2(+)·ClO4(-)·C6H5NO2, was crystallized from an aqueous solution of equimolar quantities of perchloric acid and pyridine-2-carboxylic acid. Differential scanning calorimetry (DSC) measurements show that the compound undergoes a reversible phase transition at about 261.7â K, with a wide heat hysteresis of 21.9â K. The lower-temperature polymorph (denoted LT; T = 223â K) crystallizes in the space group C2/c, while the higher-temperature polymorph (denoted RT; T = 296â K) crystallizes in the space group P2/c. The relationship between these two phases can be described as: 2a(RT) = a(LT); 2b(RT) = b(LT); c(RT) = c(LT). The crystal structure contains an infinite zigzag hydrogen-bonded chain network of 2-carboxypyridinium cations. The most distinct difference between the higher (RT) and lower (LT) temperature phases is the change in dihedral angle between the planes of the carboxylic acid group and the pyridinium ring, which leads to the formation of different ten-membered hydrogen-bonded rings. In the RT phase, both the perchlorate anions and the hydrogen-bonded H atom within the carboxylic acid group are disordered. The disordered H atom is located on a twofold rotation axis. In the LT phase, the asymmetric unit is composed of two 2-carboxypyridinium cations, half an ordered perchlorate anion with ideal tetrahedral geometry and a disordered perchlorate anion. The phase transition is attributable to the order-disorder transition of half of the perchlorate anions.