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.
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
AIMS: This study was launched to identify the SHMT2 associated Human Cancer subtypes. BACKGROUND: Cancer is the 2nd leading cause of death worldwide. Previous reports revealed the limited involvement of SHMT2 in human cancer. In the current study, we comprehensively analyzed the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. OBJECTIVE: We aim to comprehensively analyze the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Earlier, limited knowledge exists in the medical literature regarding the involvement of Serine Hydroxymethyltransferase 2 (SHMT2) in human cancer. METHODS: In the current study, we comprehensively analyzed the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Pan-cancer transcriptional expression profiling of SHMT2 was done using UALCAN while further validation was performed using GENT2. For translational profiling of SHMT2, we utilized Human Protein Atlas (HPA) platform. Promoter methylation, genetic alteration, and copy number variations (CNVs) profiles were analyzed through MEXPRESS and cBioPortal. Survival analysis was carried out through Kaplan-Meier (KM) plotter platform. Pathway enrichment analysis of SHMT2 was performed using DAVID, while the gene-drug network was drawn through CTD and Cytoscape. Furthermore, in the tumor microenvironment, a correlation between tumor purity, CD8+ T immune cells infiltration, and SHMT2 expression was accessed using TIMER. RESULTS: SHMT2 was found overexpressed in 24 different subtypes of human cancers and its overexpression was significantly associated with the reduced Overall survival (OS) and Relapse-free survival durations of Breast cancer (BRCA), Kidney renal papillary cell carcinoma (KIRP), Liver hepatocellular carcinoma (LIHC), and Lung adenocarcinoma (LUAD) patients. This implies that SHMT2 plays a significant role in the development and progression of these cancers. We further noticed that SHMT2 was also up-regulated in BRCA, KIRP, LIHC, and LUAD patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of SHMT2 enriched genes in five diverse pathways. Furthermore, we also explored some interesting correlations between SHMT2 expression and promoter methylation, genetic alterations, CNVs, tumor purity, and CD8+ T immune cell infiltrates. CONCLUSION: Our results suggested that overexpressed SHMT2 is correlated with the reduced OS and RFS of the BRCA, KIRP, LIHC, and LUAD patients and can be a potential diagnostic and prognostic biomarker for these cancers.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias de la Mama , Carcinoma Hepatocelular , Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Femenino , Variaciones en el Número de Copia de ADN , Microambiente Tumoral/genéticaRESUMEN
OBJECTIVES: Using different online available databases and Bioinformatics tools, we extensively studied the role STAT1 across different cancers. METHODS: STAT1 mRNA, protein expression, and promoter methylation were analyzed and validated using UALCAN, GENT2, Human Protein Atlas (HPA), and MEXPRESS. Furthermore, the potential prognostic values were evaluated through KM plotter. Then, cBioPortal was utilized to examine the STAT1-related genetic mutations, while pathway enrichment analysis was performed using DAVID. To identify STAT1 targeted microRNAs (miRNAs) and transcription factors (TFs) we used Enricher. Moreover, a correlational analysis between STAT1 expression tumor purity and CD8+ T immune cells and a gene-drug interaction network analysis was performed using TIMER, CTD, and Cytoscape. RESULTS: In 23 major human cancers, STAT1 expression was notably up-regulated relative to corresponding controls. As well, the elevated expression of STAT1 was exclusively found to be associated with the reduced overall survival (OS) of Esophageal Carcinoma (ESCA), Kidney Renal Clear Cell Carcinoma (KIRC), and Lung adenocarcinoma (LUAD) patients. This implies that STAT1 plays a significant role in the development and progression of these three cancers. Further pathway analysis indicated that STAT1 enriched genes were involved in six critical pathways, while a few interesting correlations were also documented between STAT1 expression and promoter methylation level, tumor purity, CD8+ T immune cells infiltration, and genetic alteration. In addition, we have also predicted a few miRNAs, TFs, and chemotherapeutic drugs that could regulate the STAT1 expression. CONCLUSION: The current study revealed the shared oncogenic, diagnostic, and prognostic role of STAT1 in ESCA, KIRC, and LUAD.
