RESUMO
BACKGROUND: Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown. METHODS: Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis. RESULTS: The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cellsãMacrophages M2ãCD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers. CONCLUSIONS: We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.
Assuntos
Biomarcadores Tumorais , Neoplasias , Microambiente Tumoral , Enzimas de Conjugação de Ubiquitina , Humanos , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Imunoterapia , Feminino , Melanoma/genética , Melanoma/imunologia , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/metabolismo , Antígeno CTLA-4/genética , Neoplasias Uveais , Antígeno B7-H1RESUMO
OBJECTIVES: The inflammatory response is a key mechanism of neuronal damage and loss during acute ischemic stroke. Hypothermia has shown promise as a treatment for ischemic stroke. In this study, we investigated the molecular signaling pathways in ischemic stroke after hypothermia treatment. METHODS: Cyclin-dependent kinase 5 (CDK5) was overexpressed or silenced in cultured cells. Nuclear transcription factor-κB (NF-κB) activity was assessed by measurement of the luciferase reporter gene. An ischemic stroke model was established in Sprague-Dawley (SD) rats using the suture-occluded method. Animals were assigned to three groups: sham operation control, ischemic stroke, and ischemic stroke + hypothermia treatment groups. Interleukin 1ß (IL-1ß) levels in the culture supernatant and blood samples were assessed by ELISA. Protein expression was measured by Western blotting. RESULTS: In HEK293 cells and primary cortical neuronal cultures exposed to hypothermia, CDK5 overexpression was associated with increased IL-1ß, caspase 1, and NF-κB levels. In both a murine model of stroke and in patients, increased IL-1ß levels were observed after stroke, and hypothermia treatment was associated with lower IL-1ß levels. Furthermore, hypothermia-treated patients showed significant improvement in neurophysiological functional outcome. CONCLUSIONS: Overall, hypothermia offers clinical benefit, most likely through its effects on the inflammatory response.
Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/terapia , Quinase 5 Dependente de Ciclina/sangue , Hipotermia Induzida/métodos , Inflamação/sangue , Interleucina-1beta/sangue , NF-kappa B/sangue , Doença Aguda , Animais , Biomarcadores/sangue , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
OBJECTIVES: The inflammatory response is a key mechanism of neuronal damage and loss during acute ischemic stroke. Hypothermia has shown promise as a treatment for ischemic stroke. In this study, we investigated the molecular signaling pathways in ischemic stroke after hypothermia treatment. METHODS: Cyclin-dependent kinase 5 (CDK5) was overexpressed or silenced in cultured cells. Nuclear transcription factor-κB (NF-κB) activity was assessed by measurement of the luciferase reporter gene. An ischemic stroke model was established in Sprague-Dawley (SD) rats using the suture-occluded method. Animals were assigned to three groups: sham operation control, ischemic stroke, and ischemic stroke + hypothermia treatment groups. Interleukin 1β (IL-1β) levels in the culture supernatant and blood samples were assessed by ELISA. Protein expression was measured by Western blotting. RESULTS: In HEK293 cells and primary cortical neuronal cultures exposed to hypothermia, CDK5 overexpression was associated with increased IL-1β, caspase 1, and NF-κB levels. In both a murine model of stroke and in patients, increased IL-1β levels were observed after stroke, and hypothermia treatment was associated with lower IL-1β levels. Furthermore, hypothermia-treated patients showed significant improvement in neurophysiological functional outcome. CONCLUSIONS: Overall, hypothermia offers clinical benefit, most likely through its effects on the inflammatory response.