RESUMO
BACKGROUND: RNASEH1 (Ribonuclease H1) encodes an endonuclease that specifically degrades the RNA of RNA-DNA hybrids and acts in DNA replication and repair. Although there are many studies on RNASEH1, the research of RNASEH1 in cancers is still insufficient. Therefore, in order to clarify the physiological mechanism of RNASEH1 in tumor cells, we evaluated the role of RNASEH1 by combining The Cancer Genome Atlas (TCGA) pan-cancer data and Genotype-Tissue Expression (GTEx) normal tissue data. METHODS: RNASEH1 expression was analyzed by using RNAseq data from TCGA and the GTEx database. The Human Protein Atlas (HPA), GeneCards and STRING database were used to explore the protein information of RNASEH1. The prognostic value of RNASEH1 was analyzed by using the clinical survival data from TCGA. Differential analysis of RNASEH1 in different cancers was performed by using R package "DESeq2", and enrichment analysis of RNASEH1 was conducted by using R package "clusterProfiler". We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases, and the correlation analysis between immune cell infiltration levels and RNASEH1 expression was performed. Not only that, we further evaluated the association of RNASEH1 with immune activating genes, immunosuppressive genes, chemokines and chemokine receptors. At the end of the article, the differential expression of RNASEH1 in pan-cancer was validated by using GSE54129, GSE40595, GSE90627, GSE106937, GSE145976 and GSE18672, and qRT-PCR was also performed for verification. FINDINGS: RNASEH1 was significantly overexpressed in 19 cancers and the overexpression was closely correlated with poor prognosis. Moreover, the expression of RNASEH1 was significantly correlated with the regulation of the tumor microenvironment. In addition, RNASEH1 expression was closely associated with immune cell infiltration, immune checkpoints, immune activators, immunosuppressive factors, chemokines and chemokine receptors. Finally, RNASEH1 also was closely associated with DNA-related physiological activities and mitochondrial-related physiological activities. INTERPRETATION: Our studying suggests that RNASEH1 is a potential cancer biomarker. And RNASEH1 may be able to regulate the tumor microenvironment by regulating the relevant physiological activities of mitochondrial and thereby regulating the occurrence and development of tumors. Thus, it could be used to develop new-targeted drugs of tumor therapy.
Assuntos
Neoplasias , Ribonuclease H , Microambiente Tumoral , Humanos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/mortalidade , Neoplasias/patologia , Ribonuclease H/análise , Ribonuclease H/genética , Expressão Gênica , Mutação , Metilação de DNA , Prognóstico , Análise de Sobrevida , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologiaRESUMO
The multiplicity of epidemiological scenarios shown by Chagas Disease, derived from multiple transmission routes of the aetiological agent, occurring on multiple geo-ecobiosocial settings determines the complexity of the disease and reveal the difficulties for its control. From the first description of the link between the parasite, the vector and its domestic habitat and the disease that Carlos Chagas made in 1909, the epidemiological scenarios of the American Trypanosomiasis has shown a dynamic increasing complexity. These scenarios changed with time and geography because of new understandings of the disease from multiple studies, because of policies change at the national and international levels and because human movements brought the parasite and vectors to new geographies. Paradigms that seemed solid at a time were broken down, and we learnt about the global dispersion of Trypanosoma cruzi infection, the multiplicity of transmission routes, that the infection can be cured, and that triatomines are not only a health threat in Latin America. We consider the multiple epidemiological scenarios through the different T. cruzi transmission routes, with or without the participation of a Triatominae vector. We then consider the scenario of regions with vectors without the parasite, to finish with the consideration of future prospects.
Assuntos
Doença de Chagas , Triatominae , Trypanosoma cruzi , Animais , Doença de Chagas/parasitologia , Vetores de Doenças , Ecossistema , Humanos , Triatominae/parasitologiaRESUMO
The multiplicity of epidemiological scenarios shown by Chagas Disease, derived from multiple transmission routes of the aetiological agent, occurring on multiple geo-ecobiosocial settings determines the complexity of the disease and reveal the difficulties for its control. From the first description of the link between the parasite, the vector and its domestic habitat and the disease that Carlos Chagas made in 1909, the epidemiological scenarios of the American Trypanosomiasis has shown a dynamic increasing complexity. These scenarios changed with time and geography because of new understandings of the disease from multiple studies, because of policies change at the national and international levels and because human movements brought the parasite and vectors to new geographies. Paradigms that seemed solid at a time were broken down, and we learnt about the global dispersion of Trypanosoma cruzi infection, the multiplicity of transmission routes, that the infection can be cured, and that triatomines are not only a health threat in Latin America. We consider the multiple epidemiological scenarios through the different T. cruzi transmission routes, with or without the participation of a Triatominae vector. We then consider the scenario of regions with vectors without the parasite, to finish with the consideration of future prospects.