Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma

Summary:Cancer testis(CT)antigens have received particular attention in cancer immunotherapy.OY-TES-1 is a member of CT antigens.This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma(HCC).OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR(RT-PCR).Of the 56 cases of HCC tissues tested,37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR.OY-TES-1 protein was subsequently observed on a panel of tissue microarrays.Sera from patients were tested for OY-TES-1 antibody by ELISA.To identify OY-TES-1 capable of inducing cellular immune response,OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro.The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56(73.21%)HCC tissues,whereas none in 5 normal liver tissues.OY-TES-1 mRNA was frequently expressed not only in HCC tissues(72.97%,27/37),but also in paired adjacent non-cancer tissues(64.86%,24/37).But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues(0.76854 vs.0.09834,P=0.021).Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues,and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues.Seropositivity was detected in 10 of the 45 HCC patients,but not detected in 17 cirrhosis patients and 76 healthy donors.The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2^+HCC cell line which expressed OY-TES-1.The target lysis was mainly HLA class I-dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule.In summary,OY-TES-1 expression is upregulated in HCC tissues and can be recognized by humoral and cellular responses,which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.

FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy

Objective:Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer,but not in normal tissues except for testis.This study aimed to investigate the expression and functional role of FMR1NB in glioma.Methods:The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry,respectively,in glioma specimens from 83 patients at follow-up.The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines Al 72 and U251.Results:FMR1NB mRNA and protein expression was detected in 58.8%(77/131)and 46.34%(57/123)of glioma tissues,respectively.FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome.Knockdown of FMR1NB induced apoptosis and suppressed proliferation,adhesion,migration,and invasion by modulating the expression of cyclin A,CDK2,caspase-3,E-cadherin,and N-cadherin in A172 and U251 cells.Conclusion:Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.

High Expression of Fibronectin 1 Predicts a Poor Prognosis in Glioblastoma

Objective Glioblastoma multiforme(GBM),the most malignant intracranial neoplasm,is associated with a high mortality and recurrence rate due to the aggressive nature and heterogeneity of the tumor.Some of the molecular markers involved in the tumorigenesis of GBM are essential in prognosis,diagnosis,and treatment.Due to the limitations of therapeutic effects,this study aims to explore novel biomarkers with prognostic value and to provide new insights into therapeutic targets.Methods The expression profile of mRNAs in GBM was detected by RNA-sequencing,and differentially expressed genes were identified by integrating the data from RNA-seq results and the GEPIA2 database.Of the total 40 hub genes,FN1,P4HB,and PPIB showed prognostic significance based on both GEPIA2 and CGGA databases.The validation of FN1,P4HB,and PPIB expression by qPCR and correlation analysis with clinicopathological features were performed in 41 GBM tissues from our institution.Results Kaplan-Meier analysis revealed that FN1 and P4HB expressions levels were related to the overall survival(OS)of GBM patients(P<0.05).Multivariate analysis showed that FN1 overexpression(HR=9.199,P=0.002)was an independent and unfavorable prognostic factor for GBM patients.The median survival time was 8.5 months and 21 months for high and low expressions of FN1,respectively.Conclusion It was suggested that FN1 could be an ideal target for prognosis and a potential therapeutic target in GBM.

Microrna-1224-5p Is a Potential Prognostic and Therapeutic Biomarker in Glioblastoma:Integrating Bioinformatics and Clinical Analyses

Objective Glioblastoma(GBM)is the most common,invasive,and malignant primary brain tumor with a poor prognosis and high recurrence rate.It’s known that some microRNAs(miRNAs)which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM.This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker.Methods Differentially expressed miRNAs(DEmiRNAs)were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus(GEO)database through bioinformatics tools.The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas(CGGA).Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database.TAM2.0 database,Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways analysis were used to analyze the function of the dysregulated miRNAs.Subsequently,protein-protein interaction(PPI)network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs,respectively.Then,core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks.Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues.Furthermore,the potential biomarkers were identified by clinical correlation analysis and survival analysis.Results Totally,68 intersecting DEmiRNAs were identified,40 of which were upregulated and the other 28 miRNAs were downregulated.Two upregulated and 4 downregulated miRNAs showed prognostic significance.Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p,which were respectively upregulated and downregulated in GBM.The correlation between miR-1224-5p level and recurrence was statistically significant(P=0.011).Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis.Moreover,high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis.Conclusion MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.

基于个体化机器学习的原发性免疫性血小板减少症危重出血预测模型:一项全国前瞻性队列研究

原发性免疫性血小板减少症(ITP)中少见但至关重要的危重出血事件,给患者的预后、生活质量和治疗决策带来严重影响。尽管有一些研究探讨了ITP中与危重出血相关的风险因素,但目前尚缺乏大样本数据、大规模多中心研究结果以及针对ITP患者致命出血事件的预测模型。本研究首次采用国际血栓与止血学会新提出的ITP致命出血标准,利用大样本数据开发了首个基于机器学习的在线应用,用于预测ITP患者的致命出血.研究中,我们使用中国各地大型多中心数据进行开发,并对全国39家医疗中心进行为期一年的外部测试,得到了较好的训练、验证和测试数据集预测能力该基于新算法的便捷网络工具能够快速识别ITP患者的出血风险,辅助临床决策,有望未来降低不良事件的发生。