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circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.
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Bases de Dados Genéticas , Neoplasias , RNA Circular , Humanos , Linhagem Celular , Neoplasias/genéticaRESUMO
Alternative splicing (AS) is assumed to play important roles in the progression and prognosis of cancer. Currently, the comprehensive analysis and clinical relevance of AS in lower-grade diffuse gliomas have not been systematically addressed. Here, we gathered alternative splicing data of lower-grade diffuse gliomas from SpliceSeq. Based on the Percent Spliced In (PSI) values of 515 lower-grade diffuse glioma patients from the Cancer Genome Atlas (TCGA), we performed subtype-differential AS analysis and consensus clustering to determine robust clusters of patients. A total of 48 050 AS events in 10 787 genes in lower-grade diffuse gliomas were profiled. Subtype-differential splicing analysis and functional annotation revealed that spliced genes were significantly enriched in numerous cancer-related biological phenotypes and signalling pathways. Consensus clustering using AS events identified three robust clusters of patients with distinguished pathological and prognostic features. Moreover, each cluster was also associated with distinct genomic alterations. Finally, we developed and validated an AS-related signature with Cox proportional hazards model. The signature, significantly associated with clinical and molecular features, could serve as an independent prognostic factor for lower-grade diffuse gliomas. Thus, our results indicated that AS events could discriminate molecular subtypes and have prognostic impact in lower-grade diffuse gliomas.
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Processamento Alternativo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , Biomarcadores Tumorais/genética , Análise por Conglomerados , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sequência de RNA , Transdução de SinaisRESUMO
1p/19q codeletion, which leads to the abnormal expression of 1p19q genes in oligodendroglioma, is associated with chemosensitivity and favorable prognosis. Here, we aimed to explore the clinical implications of 1p19q gene expression in 1p/19q non-codel gliomas. We analyzed expression of 1p19q genes in 668 1p/19q non-codel gliomas obtained from The Cancer Genome Atlas (n = 447) and the Chinese Glioma Genome Atlas (n = 221) for training and validation, respectively. The expression of 1p19q genes was significantly correlated with the clinicopathological features and overall survival of 1p/19q non-codel gliomas. Then, we derived a risk signature of 25 selected 1p19q genes that not only had prognosis value in total 1p/19q non-codel gliomas but also had prognosis value in stratified gliomas. The prognosis value of the risk signature was superior than known clinicopathological features in 1p/19q non-codel gliomas and was also highly associated with the following features: loss of CDKN2A/B copy number in mutant-IDH-astrocytoma; telomerase reverse transcriptase (TERT) promoter mutation, combined chromosome 7 gain/chromosome 10 loss and epidermal growth factor receptor amplification in wild-type-IDH-astrocytoma; classical and mesenchymal subtypes in glioblastoma. Furthermore, genes enriched in the biological processes of cell division, extracellular matrix, angiogenesis significantly correlated to the signature risk score, and this is also supported by the immunohistochemistry and cell biology experiments. In conclusion, the expression profile of 1p19q genes is highly associated with the malignancy and prognosis of 1p/19q non-codel gliomas. A 25-1p19q-gene signature has powerfully predictive value for both malignant molecular pathological features and prognosis across distinct subgroups of 1p/19q non-codel gliomas.
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Biomarcadores Tumorais/genética , Neoplasias Encefálicas/patologia , Deleção Cromossômica , Cromossomos Humanos Par 19/genética , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Movimento Celular , Proliferação de Células , Seguimentos , Glioma/genética , Glioma/cirurgia , Humanos , Pessoa de Meia-Idade , Prognóstico , RNA-Seq , Taxa de Sobrevida , Transcriptoma , Células Tumorais Cultivadas , Adulto JovemRESUMO
The methylation status of the promoter of MGMT gene is a crucial factor influencing clinical decision-making in patients with gliomas. MGMT pyrosequencing results are often dichotomized by a cut-off value based on an average of several tested CpGs. However, this method frequently results in a "gray zone", representing a dilemma for physicians. We therefore propose a novel analytical model for MGMT methylation pyrosequencing. MGMT CpG heterogeneity was investigated in 213 glioma patients in two tested cohorts: cohort A in which CpGs 75-82 were tested and cohort B in which CpGs 72-78 were tested. The predictive performances of the novel and traditional averaging models were compared in 135 patients who received temozolomide using receiver operating characteristic curves and Kaplan-Meier curves, and in patients stratified according to isocitrate dehydrogenase gene mutation status. The results were validated in an independent cohort of 65 consecutive patients with high-grade gliomas from the Chinese Glioma Genome Atlas database. Heterogeneity of MGMT promoter CpG methylation level was observed in most gliomas. The optimal cut-off value for each individual CpG varied from 4-16%. The current analysis defined MGMT promoter methylation as occurring when at least three CpGs exceeded their respective cut-off values. This novel analysis could accurately predict the prognosis of patients in the methylation "gray zone" according to the standard averaging method, and improved the area under the curves from 0.67, 0.76, and 0.67 to 0.70, 0.84, and 0.72 in cohorts A, B, and the validation cohort, respectively, demonstrating superiority of this analytical method in all three cohorts. Furthermore, the advantages of the novel analysis were retained regardless of WHO grade and isocitrate dehydrogenase gene mutation status. In conclusion, this novel analytical model offers an improved clinical predictive performance for MGMT pyrosequencing results and is suitable for clinical use in patients with gliomas.
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Neoplasias Encefálicas/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioma/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas Supressoras de Tumor/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Resectioning of giant maxillofacial tumors has been shown to cause facial depression deformity, representing a persistent challenge for surgeons. Here, the authors review their experience using autologous free fat grafts to repair total parotidectomy defects. This review aims to encourage the surgical field to pay more attention to this century-old treatment technique. METHODS: Patients were included who underwent free fat transfer for tissue reconstruction after total parotidectomy at the Affiliated Stomatology Hospital of China Medical University between 2012 and 2018. Patients with bleeding disease or postoperative follow-up less than 6 months were excluded. RESULTS: Twenty-three patients between the ages of 35 and 68 were included in this analysis. Ten patients (6 males, 4 females) underwent fat grafting at the time of total parotidectomy, and a control group of 13 patients (9 males, 4 females) underwent total parotidectomy without correction of concave deformities. There were significant differences between fat graft group and control group in terms of age (44.9â±â9.0117 years versus 56.385â±â8.9586 years; Pâ=â0.006), Frey syndrome questionnaire score (1â±â0 versus 2.385â±â1.0439; Pâ=â0.00), blood loss (195.7â±â54.8777âmL versus 107.769â±â22.8916âmL; Pâ=â0.001), postoperative drainage (319.8â±â103.1803âmL versus 230.385â±â53.5701âmL; Pâ=â0.027), duration of postoperative drainage (122.4â±â23.8663âhours versus 90.462â±â22.2434âhours; Pâ=â0.003), and satisfaction questionnaire score (8.5â±â0.8498 versus 3â±â1.1547; Pâ=â0.00). The difference in operation time between the fat graft group and control group was not significant (417â±â108.0062âmin versus 351.538â±â91.7475âmin; Pâ=â0.131). CONCLUSION: Autologous free fat grafting resulted in more blood loss as well as an increased volume and duration of postoperative drainage. Remarkably, however, patients had superior satisfaction, lower Frey syndrome scores, and similar operation times with use of free fat grafting after parotidectomy. The authors recommend such grafting be utilized to repair concave deformities secondary to total parotidectomy.
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Tecido Adiposo/transplante , Face/cirurgia , Neoplasias Parotídeas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Tempo , Transplante AutólogoRESUMO
This study demonstrates the application of DBR structure into the remote phosphor structure to improve the angular correlated color temperature (CCT) deviation in white light-emitting diodes (WLEDs). In the experiment, the LED device with DBR structure yielded a higher luminous efficiency than a conventional structure. The CCT deviation can be improved from 1758K to 280K in a range of -70 to 70 degree and the luminous flux increases more than 10% due to the enhancement of the light extraction of the blue light. Moreover, the reflectance of the different DBR structures is analyzed with different angles to reveal the reasons of such improvements. As the result, this LED device with DBR structure shows the great potential to use as the next generation lighting source.
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BACKGROUND: The aim of this study was to investigate the efficacy of bevacizumab (Bev) in reducing peritumoral brain edema (PTBE) after stereotactic radiotherapy (SRT) for lung cancer brain metastases. METHODS: A retrospective analysis was conducted on 44 patients with lung cancer brain metastases (70 lesions) who were admitted to our oncology and Gamma Knife center from January 2020 to May 2022. All patients received intracranial SRT and had PTBE. Based on treatment with Bev, patients were categorized as SRT + Bev and SRT groups. Follow-up head magnetic resonance imaging was performed to calculate PTBE and tumor volume changes. The edema index (EI) was used to assess the severity of PTBE. Additionally, the extent of tumor reduction and intracranial progression-free survival (PFS) were compared between the two groups. RESULTS: The SRT + Bev group showed a statistically significant difference in EI values before and after radiotherapy (p = 0.0115), with lower values observed after treatment, but there was no difference in the SRT group (p = 0.4008). There was a difference in the distribution of EI grades in the SRT + Bev group (p = 0.0186), with an increased proportion of patients at grades 1-2 after radiotherapy, while there was no difference in the SRT group (p > 0.9999). Both groups demonstrated a significant reduction in tumor volume after radiotherapy (p < 0.05), but there was no difference in tumor volume changes between the two groups (p = 0.4089). There was no difference in intracranial PFS between the two groups (p = 0.1541). CONCLUSION: Bevacizumab significantly reduces the severity of PTBE after radiotherapy for lung cancer. However, its impact on tumor volume reduction and intracranial PFS does not reach statistical significance.
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Edema Encefálico , Neoplasias Encefálicas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/etiologia , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Edema Encefálico/patologia , Estudos Retrospectivos , Radiocirurgia/métodos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundárioRESUMO
Key Clinical Message: Temporal percutaneous transhepatic duodenum drainage (PTDD) seems to be effective in the treatment of postoperative afferent loop syndrome (ALS) following transverse loop colostomy for obstructive colorectal cancer. Abstract: Management of obstructive colorectal cancer still remains a challenge. There are various options with different risks of mortality and mobility for obstructive colorectal cancer. A rare unexpected postoperative ALS following a low anterior resection and transverse loop colostomy for obstructive colorectal cancer is presented in this report. A 64-year-old man had the acute ALS had been noted 10 days after transverse loop colostomy. An option was temporal PTDD treatment in the patient with history of Billroth's operation II for upper gastrointestinal bleeding 30 years ago. Acute ALS was treated by temporal PTDD. The drainage tube for PTDD was not removed until closure of the transverse colostomy 2 months later. The patient recovered uneventfully. Acute ALS after transverse loop colostomy for obstructive colorectal cancer is rare and has never been reported in the literature. The mechanism of acute ALS after construction of a loop colostomy and the treatment strategy of PTDD for acute ALS is presented.
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BACKGROUND: Dysregulated receptor tyrosine kinases, such as the mesenchymal-epidermal transition factor (MET), have pivotal role in gliomas. MET and its interaction with the tumor microenvironment have been previously implicated in secondary gliomas. However, the contribution of MET gene to tumor cells' ability to escape immunosurveillance checkpoints in primary gliomas, especially in glioblastoma (GBM), which is a WHO grade 4 glioma with the worst overall survival, is still poorly understood. METHODS: We investigated the relationship between MET expression and glioma microenvironment by using multiomics data and aimed to understand the potential implications of MET in clinical practice through survival analysis. RNA expression data from a total of 1243 primary glioma samples (WHO grades 2-4) were assembled, incorporating The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and GSE16011 data sets. RESULTS: Pearson's correlation test from the three data sets indicated that MET showed a robust correlation with programmed death-ligand 1 (PD-L1) and STAT pathways. Western blot analysis revealed that in GBM cell lines (N33 and LN229), PD-L1 and phosphorylated STAT4 were upregulated by MET activation treatment with hepatocyte growth factor and were downregulated on MET suppression by PLB-1001. Tumor tissue microarray analysis indicated a positive correlation between MET and PD-L1 and macrophage-associated markers. Chromatin immunoprecipitation-PCR assay showed enrichment of STAT4 in the PD-L1 DNA. Transwell co-culture and chemotaxis assays revealed that knockdown of MET in GBM cells inhibited macrophage chemotaxis. Moreover, we performed CIBERSORTx and single-cell RNA sequencing data analysis which revealed an elevated number of macrophages in glioma samples with MET overexpression. Kaplan-Meier survival analysis indicated that activation of the MET/STAT4/PD-L1 pathway and upregulation of macrophages were associated with shorter survival time in patients with primary GBM. CONCLUSIONS: These data indicated that the MET-STAT4-PD-L1 axis and tumor-associated macrophages might enforce glioma immune evasion and were associated with poor prognosis in GBM samples, suggesting potential clinical strategies for targeted therapy combined with immunotherapy in patients with primary GBM.
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Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/imunologia , Glioblastoma/imunologia , Macrófagos/imunologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Fator de Transcrição STAT4/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Feminino , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Macrófagos/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/imunologia , Fator de Transcrição STAT4/genética , Fator de Transcrição STAT4/imunologia , Transdução de Sinais/imunologia , Evasão TumoralRESUMO
Gliomas are the most common type of primary brain tumor in adults with a high mortality rate. Low-grade gliomas progress to glioblastoma multiforme (GBM) in the majority of cases, forming secondary GBM (sGBM), followed by rapid fatal clinical outcomes. Protein tyrosine phosphatase receptor type Z1 (PTPRZ1)-MET proto-oncogene receptor tyrosine kinase (MET) (ZM) fusion has been identified as a biomarker for sGBM that is involved in glioma progression, but the mechanism of gliomagenesis and pathology of ZM-negative sGBM has remained to be fully elucidated. A whole-transcriptome signature is thus required to improve the outcome prediction for patients with sGBM without ZM fusion. In the present study, whole-transcriptome sequencing on 42 sGBM samples with or without ZM fusion from the Chinese Glioma Genome Atlas database identified mRNAs with differential expression between patients with and without ZM fusion and the most significant survival-associated genes were identified. A 6-gene signature was identified as a novel prognostic model reflecting survival probability in patients with ZM-negative sGBM. Clinical characteristics in patients with a high or low risk score value were analyzed with the Kaplan-Meier method and a two-sided log-rank test. In addition, ZM-negative sGBM patients with a high risk score exhibited an increase in immune cells, NF-κB-induced pathway activation and a decrease in endothelial cells compared with those with a low risk score. The present study demonstrated the potential use of a next-generation sequencing-based cancer gene signature in patients with ZM-negative sGBM, indicating possible clinical therapeutic strategies for further treatment of such patients.
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Transcriptomic data derived from bulk sequencing have been applied to delineate the tumor microenvironment (TME) and define immune subtypes in various cancers, which may facilitate the design of immunotherapy treatment strategies. We herein gathered published gene expression data from diffuse lower-grade glioma (LGG) patients to identify immune subtypes. Based on the immune gene profiles of 402 LGG patients from The Cancer Genome Atlas, we performed consensus clustering to determine robust clusters of patients, and evaluated their reproducibility in three Chinese Glioma Genome Atlas cohorts. We further integrated immunogenomics methods to characterize the immune environment of each subtype. Our analysis identified and validated three immune subtypes-Im1, Im2, and Im3-characterized by differences in lymphocyte signatures, somatic DNA alterations, and clinical outcomes. Im1 had a higher infiltration of CD8+ T cells, Th17, and mast cells. Im2 was defined by elevated cytolytic activity, exhausted CD8+ T cells, macrophages, higher levels of aneuploidy, and tumor mutation burden, and these patients had worst outcome. Im3 displayed more prominent T helper cell and APC coinhibition signatures, with elevated pDCs and macrophages. Each subtype was associated with distinct somatic alterations. Moreover, we applied graph structure learning-based dimensionality reduction to the immune landscape and revealed significant intracluster heterogeneity with Im2 subtype. Finally, we developed and validated an immune signature with better performance of prognosis prediction. Our results demonstrated the immunological heterogeneity within diffuse LGG and provided valuable stratification for the design of future immunotherapy.
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Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Glioma/imunologia , Glioma/patologia , Adulto , Neoplasias Encefálicas/genética , Análise por Conglomerados , Feminino , Genoma Humano , Glioma/genética , Humanos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Gradação de Tumores , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
Glioma is a fatal brain tumor characterized by rapid proliferation and treatment resistance. Ferroptosis is a newly discovered programmed cell death and plays a crucial role in the occurrence and progression of tumors. In this study, we identified ferroptosis specific markers to reveal the relationship between ferroptosis-related genes and glioma by analyzing whole transcriptome data from Chinese Glioma Genome Atlas, The Cancer Genome Atlas dataset, GSE16011 dataset, and the Repository of Molecular Brain Neoplasia Data dataset. Nineteen ferroptosis-related genes with clinical and pathological features of glioma were identified as highly correlated. Functional assays in glioma cell lines indicated the association of ferroptosis with temozolomide resistance, autophagy, and glioma cell migration. Therefore, the identified ferroptosis-related genes were significantly correlated with glioma progression.
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AIMS: The pyrosequencing (PSQ) has been regarded as the gold standard for MGMT promoter methylation testing in gliomas. However, various CpG combinations are currently used in clinical practice. We aimed to clarify how and how many CpGs combined is robust enough to predict MGMT mRNA expression and therapeutic prognosis of patients. METHODS: Total 223 patients with WHO III/IV gliomas were enrolled from Chinese Glioma Genome Atlas, including two independent cohorts, the eight-site cohort (with CpGs 75-82 tested) and the seven-site cohort (with CpGs 72-78 tested). Spearman's correlation and ROC curves were employed to investigate the value of different CpG combinations on predicting MGMT mRNA expression. The ROC curves and Kaplan-Meier steps were performed to compare the TMZ therapeutic prognostic values of different CpG combinations. RESULTS: The methylation level of all individual CpG and CpG combinations for the eleven CpGs (CpGs 72-82), significantly correlated to MGMT mRNA expression (Spearman, all P < 0.0001), could effectively predict the mRNA expression (AUC, 0.86-0.91 in the eight-site cohort, 0.83-0.90 in the seven-site cohort). Moreover, the correlation coefficients and the predictive values presented equivalent when four or more CpGs combinedly used (AUC, 0.88-0.90 in the eight-site cohort, 0.87-0.88 in the seven-site cohort). Finally, similar results were also observed when using selected CpG combinations to predict therapeutic prognosis of patients. CONCLUSIONS: Four-CpG combinations of pyrosequencing are sufficient for evaluating the methylation status of MGMT and predicting therapeutic prognosis in gliomas.
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Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/metabolismo , Ilhas de CpG , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Glioma/metabolismo , Temozolomida/uso terapêutico , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Biomarcadores Tumorais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Estudos de Coortes , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Expressão Gênica , Glioma/genética , Glioma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Proteínas Supressoras de Tumor/genética , Adulto JovemRESUMO
BACKGROUND: Glioma is the most common and aggressive type of primary brain tumor in adults. Although radiotherapy and chemotherapy are used in the treatment of glioma, survival remains unsatisfactory. Chemoresistance is one of the primary reasons for the poor prognosis of glioma. Several studies have demonstrated that glioma stem cells (GSC) may be one of the reasons for chemoresistance. In this article, we attempt to search for a new biomarker related to GSC and chemoresistance in glioma. METHODS: We used three datasets (GSE23806, COSMIC, and CGGA) to search for the genes related to GSC, temozolomide (TMZ) resistance, and overall survival. The selected gene was investigated with respect to the relationship between mRNA levels and clinical characteristics in the CGGA and TCGA dataset. Gene ontology (GO) analysis was used for bioinformatics analysis. Kaplan-Meier survival analysis and Cox regression analysis were used for survival analysis. RESULTS: The transmembrane protein 71 (TMEM71) gene was selected for further research. TMEM71 was highly expressed in GSCs and TMZ-resistant cells. The TMEM71 mRNA levels increased with increasing grades of glioma. In IDH-wild-type and MGMT-unmethylated samples, TMEM71 was overexpressed. The TMEM71 transcript levels were also increased significantly in mesenchymal subtype gliomas. GO analysis demonstrated that TMEM71 was related to the immune and inflammatory responses, cell proliferation, cell migration, chemotaxis, and the response to drugs. Specifically, PD-1, PD-L1, TIM-3, and B7-H3 were tightly associated with TMEM71 expression. This result indicates that TMEM71 may play an important role in the immune response. More importantly, high expression of TMEM71 was correlated with short survival time in both glioma and glioblastoma patients. CONCLUSION: In summary, TMEM71 expression was increased in GBM and associated with immune response. Our study suggests that TMEM71 may function as an oncogene and serve as a new effective therapeutic target for the treatment of glioma.
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Biomarcadores Tumorais/biossíntese , Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Proteínas de Membrana/biossíntese , Transcrição Gênica/fisiologia , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Bases de Dados Genéticas , Glioma/genética , Humanos , Proteínas de Membrana/genéticaRESUMO
BACKGROUND: Researches on immunotherapy of glioblastoma multiforme (GBM, WHO grade IV) have increased exponentially in recent years. As a targeted therapy, a series of biomarkers have been identified in local tumor tissue, while circulating marker which could be detected in the body fluids is still lacking. ADAMTSL4, a secreted glycoprotein, was earlier found to play a critical role in a prognostic signature for primary GBM (pGBM). We aimed to investigate the role of ADAMTSL4 at transcriptome level and its relationship with clinical practice in pGBM. METHODS: A cohort of 88 pGBM patients with RNA-seq data from the Chinese Glioma Genome Atlas (CGGA) was analyzed, and 168 pGBM patients from TCGA were included as validation. Several bioinformatic methods and predictive tools were applied to investigate the ADAMTSL4-associated immune microenvironment status. RESULTS: We found that ADAMTSL4 was enriched in GBM (WHO grade IV), especially for those with IDH1/2 wild-type and MGMT unmethylated groups. According to the TCGA classification scheme, ADAMTSL4 can act as a potential marker for subtypes with poorer prognosis. Bioinformatic analyses revealed that ADAMTSL4 was significantly correlated to the immune-related processes in GBM (WHO grade IV), especially representing the infiltration of immune cells and complicated tumor microenvironment. Clinically, high expression of ADAMTSL4 was an independent indicator for poor prognosis. CONCLUSION: The expression of ADAMTSL4 is closely related to the clinicopathologic characteristics of pGBM. Meanwhile, it may play a critical role in immune-related processes. As a secreted glycoprotein, ADAMTSL4 is a promising circulating biomarker for pGBM, deserving further investigations.
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Proteínas ADAMTS/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteínas ADAMTS/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Encéfalo/metabolismo , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/patologia , Criança , Feminino , Glioblastoma/sangue , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Aberrant expression of RNA processing genes may drive the alterative RNA profile in lower-grade gliomas (LGGs). Thus, we aimed to further stratify LGGs based on the expression of RNA processing genes. METHODS: This study included 446 LGGs from The Cancer Genome Atlas (TCGA, training set) and 171 LGGs from the Chinese Glioma Genome Atlas (CGGA, validation set). The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was conducted to develop a risk-signature. The receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used to study the prognosis value of the risk-signature. RESULTS: Among the tested 784 RNA processing genes, 276 were significantly correlated with the OS of LGGs. Further LASSO Cox regression identified a 19-gene risk-signature, whose risk score was also an independently prognosis factor (P<0.0001, multiplex Cox regression) in the validation dataset. The signature had better prognostic value than the traditional factors "age", "grade" and "WHO 2016 classification" for 3- and 5-year survival both two datasets (AUCs > 85%). Importantly, the risk-signature could further stratify the survival of LGGs in specific subgroups of WHO 2016 classification. Furthermore, alternative splicing events for genes such as EGFR and FGFR were found to be associated with the risk score. mRNA expression levels for genes, which participated in cell proliferation and other processes, were significantly correlated to the risk score. CONCLUSIONS: Our results highlight the role of RNA processing genes for further stratifying the survival of patients with LGGs and provide insight into the alternative splicing events underlying this role.
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Regulação Neoplásica da Expressão Gênica , Glioma/genética , Splicing de RNA/genética , Transcriptoma , Adenosina Trifosfatases/genética , Sequência de Bases , Linhagem Celular Tumoral , Biologia Computacional , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Glioma/metabolismo , Glioma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Biologia Molecular , Análise Multivariada , Prognóstico , Splicing de RNA/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Regressão , Análise de Sobrevida , Fatores de Transcrição/genéticaRESUMO
AIMS: To investigate the role of LINC00152 in high-grade glioma (HGG). METHODS: We collected data from the Chinese Glioma Genome Atlas (CGGA) microarray, CGGA RNA sequencing, and GSE16011 datasets to evaluate the expression and prognostic relationship of LINC00152 in patients with HGGs. A knockdown assay was performed to determine the function of LINC00152 in glioma development and progression in vitro and in vivo. RESULTS: The expression of LINC00152 was increased with glioma grade, especially in the mesenchymal TCGA subtype. LINC00152 was independently associated with poor prognosis, and the overall survival (OS) of the high expression group was shorter than the low expression group (median OS 14.77 vs 9.65 months; P = 0.0216) in the CGGA microarray dataset. The results were validated in the other 2 datasets. Based on the expression of LINC00152, 4288 (2519 positively; 1769 negatively) probes were extracted to perform a biological process analysis using the Database for Annotation, Visualization, and Integrated Discovery. Positively regulated genes were enriched in immune response, apoptotic process, cell adhesion, and regulation of cell proliferation. The clinical and molecular features of HGG patients indicated that patients in the LINC00152 high expression group tended to display the mesenchymal type, older (≥46 years), isocitrate dehydrogenase1 wild-type, O(6)-methylguanine DNA methyltransferase unmethylated, nonchemotherapy, and low karnofsky performance status. Functionally, knockdown of LINC00152 inhibited cell proliferation, migration, and invasion and increased the sensitivity of chemotherapy in vitro. CONCLUSION: Our results indicate that knockdown of LINC00152 could inhibit tumor growth in vivo. LINC00152 could serve as a potential prognostic biomarker in patients with HGG.
Assuntos
Neoplasias Encefálicas/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioma/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Neoplasias Encefálicas/diagnóstico , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Glioma/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos Nus , Análise em Microsséries , Invasividade Neoplásica/genética , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução Genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Correction for 'A high quality liquid-type quantum dot white light-emitting diode' by Chin-Wei Sher et al., Nanoscale, 2016, 8, 1117-1122.
RESUMO
This study demonstrates a novel package design to store colloidal quantum dots in liquid format and integrate them with a standard LED. The high efficiency and high quality color performance at a neutral white correlated color temperature is demonstrated. The experimental results indicate that the liquid-type quantum dot white light-emitting diode (LQD WLED) is highly efficient and reliable. The luminous efficiency and color rendering index (CRI) of the LQD WLED can reach 271 lm Wop(-1) and 95, respectively. Moreover, a glass box is employed to prevent humidity and oxygen erosion. With this encapsulation design, our quantum dot box can survive over 1000 hours of storage time.
RESUMO
Aberrant c-Met has been implicated in the development of many cancers. The objective of this study was to identify an unfavorable prognostic marker that might guide decisions regarding clinical treatment strategies for high-grade gliomas. C-Met expression was measured using immunohistochemistry in 783 gliomas, and we further analyzed c-Met mRNA levels using the Agilent Whole Genome mRNA Microarray in 286 frozen samples. In vitro, we performed cell migration and invasion assays. Cell sensitivity to temozolomide (TMZ) chemotherapy was determined using MTT assays. Both mRNA and protein levels of c-Met were significantly associated with tumor grade progression and inversely correlated with overall and progression-free survival in high-grade gliomas (all P < 0.0001). These findings were nearly consistent at the mRNA level across 3 independent cohorts. Multivariable analysis indicated that c-Met was an independent prognostic marker after adjusting for age, preoperative Karnofsky Performance Status (KPS) score, the extent of resection, radiotherapy, TMZ chemotherapy, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Further analysis in vitro revealed that downregulating the expression of c-Met dramatically inhibited cell migration and invasion capacities, enhanced sensitivity to TMZ chemotherapy in H4 and U87 glioma cells. Our results suggest that c-Met may serve as a potential predictive maker for clinical decision making.