RESUMEN
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.
Asunto(s)
Humanos , Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Neoplasias Hepáticas , Pronóstico , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Regulación hacia Arriba , Proteínas de Unión al ADN , Variaciones en el Número de Copia de ADNRESUMEN
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.
RESUMEN
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.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Variaciones en el Número de Copia de ADN , Proteínas de Unión al ADN , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Pronóstico , Regulación hacia ArribaRESUMEN
OBJECTIVE: It has been recently reported that Bisphenol A (BPA) may leach out into food, beverages and water samples from the plastic ware in which it is stored. Serious health hazards have been reported from BPA. The purpose of this study is to assess the BPA contents in blood and to assess the risk of cancer. METHOD: A total of 100 individuals were selected for study according to the following five age groups: 5-10, 11-20, 21-30, 31-40 and 41-50 years. They were then further divided into normal and diseased. Age, gender, education, source of drinking water, type of food, smoking habit, any exposure to chemicals and history of cancer were elicited during interview. Blood samples were collected and processed for analysis using reversed phase-high performance liquid chromatography (rp-HPLC) in isocratic mode. The mobile phase consisted of acetonitrile and water (1:1) at a flow-rate of 1 ml min-1. RESULTS: Bisphenol A contents found in blood samples of all age groups ranged from 1.53-3.98 (mean = 2.94, SD = 0.9). P-values, for the exposed people and those having a history of cancer, were < 0.05 showing a significant relationship between BPA and cancer. The United States Environmental Protection Agency (US EPA) has established a reference dose of 50 µg/L. Odd ratios and relative risk for smoking habit were < 1 while for all others they were > 1. CONCLUSION: It was concluded from the study that people using bottled water, packaged food, having a history ofcancer and who had been exposed to any type ofchemicals are at higher risk ofdisease.
OBJETIVO: Se ha reportado recientemente que el bisfenol A (BPA) puede filtrarse a alimentos, bebidas y agua, a partir de los recipientes plásticos en que aquellos se almacenan. En tal sentido, se han reportado serios casos de riesgo para la salud a causa del BPA. El propósito de este estudio es evaluar la concentración de BPA en sangre, y el consiguiente riesgo de enfermedades cancerosas. MÉTODO: Un total de 100 individuos fueron seleccionados para el estudio, de acuerdo con los siguientes cinco grupos etarios: 5-10, 11-20, 21-30, 31-40 y 41-50 años. Dichos grupos fueron divididos entonces sobre la base de sujetos normales frente a enfermos. En la entrevista se tomó nota de la edad, el género, la educación, la fuente de agua potable, el tipo de comida, el hábito de fumar, cualquier exposición a productos químicos, así como la historia de cáncer. Las muestras de sangre fueron recogidas y procesadas para realizar análisis, utilizando cromatografía líquida de alta eficacia de fase reversa (rp-HPLC) en modo isocrático. La fase móvil consistió en acetonitrilo y agua (1:1) con una tasa de flujo de 1 ml min-1. RESULTADOS: Las concentraciones de bisfenol-A halladas en las muestras de sangre de todos los grupos etarios, oscilaron de 1.53 - 3.98 (M = 2.94, SD = 0.9). Los valores P para las personas expuestas y con una historia de cáncer, fueron < 0.05, indicando una relación directa entre el BPA y el cáncer. La Agencia de Protección Ambiental de los Estados Unidos (US EPA) ha establecido una dosis de referencia de 50 µg/L. El cociente de probabilidades (odd ratios) y el riesgo relativo con respecto al hábito de fumar fueron < 1 mientras que para todos los otros casos otros fueron >1. CONCLUSIÓN: A partir del estudio se concluye que las personas que usan agua embotellada, alimentos empaquetados, así como las personas que poseen una historia de cáncer, y los individuos que habían estado expuestos a cualquier tipo de productos químicos, presentan un mayor riesgo de enfermedad.
Asunto(s)
Adolescente , Adulto , Niño , Preescolar , Humanos , Persona de Mediana Edad , Adulto Joven , Compuestos de Bencidrilo/sangre , Neoplasias/sangre , Fenoles/sangre , Oportunidad RelativaRESUMEN
OBJECTIVE: It has been recently reported that Bisphenol A (BPA) may leach out into food, beverages and water samples from the plastic ware in which it is stored. Serious health hazards have been reported from BPA. The purpose of this study is to assess the BPA contents in blood and to assess the risk of cancer. METHOD: A total of 100 individuals were selected for study according to the following five age groups: 5-10, 11-20, 21-30, 31-40 and 41-50 years. They were then further divided into normal and diseased. Age, gender, education, source of drinking water, type of food, smoking habit, any exposure to chemicals and history of cancer were elicited during interview. Blood samples were collected and processed for analysis using reversed phase-high performance liquid chromatography (rp-HPLC) in isocratic mode. The mobile phase consisted of acetonitrile and water (1:1) at a flow-rate of 1 ml min-1. RESULTS: Bisphenol A contents found in blood samples of all age groups ranged from 1.53-3.98 (mean = 2.94, SD = 0.9). P-values, for the exposed people and those having a history of cancer, were < 0.05 showing a significant relationship between BPA and cancer The United States Environmental Protection Agency (US EPA) has established a reference dose of 50 microg/L. Odd ratios and relative risk for smoking habit were < 1 while for all others they were > 1. CONCLUSION: It was concluded from the study that people using bottled water, packaged food, having a history of cancer and who had been exposed to any type of chemicals are at higher risk of disease.