目的:免疫检查点在包括人肺腺癌(lung adenocarcinoma,LUAD)的免疫治疗中取得了突破性进展,而HHLA2(Human endogenous retrovirus-H long terminal repeat-associating protein 2,人内源性逆转录病毒H长末端重复结合蛋白2)是最近发现的...目的:免疫检查点在包括人肺腺癌(lung adenocarcinoma,LUAD)的免疫治疗中取得了突破性进展,而HHLA2(Human endogenous retrovirus-H long terminal repeat-associating protein 2,人内源性逆转录病毒H长末端重复结合蛋白2)是最近发现的免疫调节分子B7同源家族的成员。本文研究HHLA2在LUAD中的表达情况和临床意义。方法:采用免疫组化方法检测74例LUAD患者及相应的癌旁组织中HHLA2的表达情况。结果:与癌旁组织相比, HHLA2在LUAD的肿瘤组织中显著过表达(P<0.05),但并未发现与其他临床病理参数的相关性。结论:HHLA2与肺腺癌的发生有关,是潜在的免疫治疗靶点。展开更多
目的:探讨人内源性逆转录病毒-H长末端重复关联蛋白2(human endogenous retrovirus subfamily H long terminal repeat associating protein 2,HHLA2)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其与HCC患者临床病理特征...目的:探讨人内源性逆转录病毒-H长末端重复关联蛋白2(human endogenous retrovirus subfamily H long terminal repeat associating protein 2,HHLA2)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其与HCC患者临床病理特征和预后的关系。方法:基于TCGA数据库分析人HCC组织中HHLA2 mRNA表达与B7家族基因的相关性,用组织芯片技术、免疫组织化学染色法分别检测90例HCC组织及其癌旁组织中HHLA2的表达。用Wilcoxon秩和检验比较HCC组织及癌旁组织中HHLA2表达水平的差异,用χ2检验分析HCC组织中HHLA2表达水平与患者临床病理特征的关系,用Kaplan-Meier法分析HHLA2表达水平与患者总生存期(OS)的关系,拟合Cox模型评价不同指标的预后价值。结果:HCC组织中HHLA2 mRNA表达水平与B7家族CD274、C10orf54、PDCD1LG2、ICOSLG和CD276相关;HCC组织中HHLA2的表达水平与肿瘤大小显著相关(χ2=4.531,P<0.05);HHLA2低表达的HCC患者OS较HHLA2高表达患者显著延长(HR=1.878,95%CI:1.066~3.309,P<0.05);多因素风险比例模型显示,肿瘤大小(HR=2.493,95%CI:1.310~4.742,P<0.01)可作为HCC患者预后评估的独立危险因素。结论:HHLA2表达与HCC患者预后显著相关,是HCC免疫治疗的潜在新靶点。展开更多
Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma(ESCC)have shown promising results.However,a comprehensive understanding of B7-CD28 family members in ESCC...Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma(ESCC)have shown promising results.However,a comprehensive understanding of B7-CD28 family members in ESCC is still limited.This study aimed to construct a novel B7-CD28 family-based prognosis system to predict survival in patients with ESCC.We collected 179 cases from our previously published microarray data and 86 cases with qPCR data.Specifically,119 microarray data(GSE53624)were used as a training set,whereas the remaining 60 microarray data(GSE53622),all 179 microarray data(GSE53625)and an independent cohort with 86 qPCR data were used for validation.The underlying mechanism and immune landscape of the system were also explored using bioinformatics and immunofluorescence.We examined 13 well-defined B7-CD28 family members and identified 2 genes(ICSOLG and HHLA2)with the greatest prognostic value.A system based on the combination HHLA2 and ICOSLG(B7-CD28 signature)was constructed to distinguish patients as high-or low-risk of an unfavorable outcome,which was further confirmed as an independent prognostic factor.As expected,the signature was well validated in the entire cohort and in the independent cohort,as well as in different clinical subgroups.The signature was found to be closely related to immune-specific biological processes and pathways.Additionally,high-risk group samples demonstrated high infiltration of Tregs and fibroblasts and distinctive immune checkpoint panels.Collectively,we built the first,practical B7-CD28 signature for ESCC that could independently identify high-risk patients.Such information may help inform immunotherapy-based treatment decisions for patients with ESCC.展开更多
系统评价人内源性逆转录病毒-H长末端重复关联蛋2(HHLA2)表达与肿瘤预后的关系。方法:计算机检索中国知网(CNKI)、万方、维普、中国生物医学文献数据库、Cochrane Library、Web of Science、PubMed及Embase数据库,纳入公开发表的有关HH...系统评价人内源性逆转录病毒-H长末端重复关联蛋2(HHLA2)表达与肿瘤预后的关系。方法:计算机检索中国知网(CNKI)、万方、维普、中国生物医学文献数据库、Cochrane Library、Web of Science、PubMed及Embase数据库,纳入公开发表的有关HHLA2表达与肿瘤预后相关性的文献,检索时限均为建库至2020年10月。由2位评价员独立筛选文献、提取资料并评价纳入研究的质量后,采用Stata12.0软件对符合条件的文献进行Meta分析。结果:共纳入11篇文献,包含1671例肿瘤病人。Meta分析结果显示,HHLA2高表达发生死亡的风险是 HHLA2低表达的1.63倍,差异有统计学意义(HR=1.63,95%CI:1.21~2.18,P=0.001)。亚组分析显示,在呼吸道肿瘤和消化道肿瘤HHLA2高表达与总生存期(OS,第一次出现,用英文全称)显著相关(HR=3.02,95%CI:1.54~5.94,P<0.01;HR=1.54,95%CI:1.02~2.31,P<0.05),在泌尿道肿瘤HHLA2高表达与OS无相关性(HR=1.30,95%CI:0.44~3.84,P>0.05)。敏感性分析显示结果稳定,纳入文献无明显发表偏倚(补充统计量值,P>0.05)。结论:HHLA2高表达与消化道和呼吸道肿瘤预后相关,与其他种类的肿瘤预后无关。但由于纳入研究的文献数量有限,该研究结果仍有待于纳入更多的研究观察和证实。展开更多
文摘目的:免疫检查点在包括人肺腺癌(lung adenocarcinoma,LUAD)的免疫治疗中取得了突破性进展,而HHLA2(Human endogenous retrovirus-H long terminal repeat-associating protein 2,人内源性逆转录病毒H长末端重复结合蛋白2)是最近发现的免疫调节分子B7同源家族的成员。本文研究HHLA2在LUAD中的表达情况和临床意义。方法:采用免疫组化方法检测74例LUAD患者及相应的癌旁组织中HHLA2的表达情况。结果:与癌旁组织相比, HHLA2在LUAD的肿瘤组织中显著过表达(P<0.05),但并未发现与其他临床病理参数的相关性。结论:HHLA2与肺腺癌的发生有关,是潜在的免疫治疗靶点。
文摘目的:探讨人内源性逆转录病毒-H长末端重复关联蛋白2(human endogenous retrovirus subfamily H long terminal repeat associating protein 2,HHLA2)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其与HCC患者临床病理特征和预后的关系。方法:基于TCGA数据库分析人HCC组织中HHLA2 mRNA表达与B7家族基因的相关性,用组织芯片技术、免疫组织化学染色法分别检测90例HCC组织及其癌旁组织中HHLA2的表达。用Wilcoxon秩和检验比较HCC组织及癌旁组织中HHLA2表达水平的差异,用χ2检验分析HCC组织中HHLA2表达水平与患者临床病理特征的关系,用Kaplan-Meier法分析HHLA2表达水平与患者总生存期(OS)的关系,拟合Cox模型评价不同指标的预后价值。结果:HCC组织中HHLA2 mRNA表达水平与B7家族CD274、C10orf54、PDCD1LG2、ICOSLG和CD276相关;HCC组织中HHLA2的表达水平与肿瘤大小显著相关(χ2=4.531,P<0.05);HHLA2低表达的HCC患者OS较HHLA2高表达患者显著延长(HR=1.878,95%CI:1.066~3.309,P<0.05);多因素风险比例模型显示,肿瘤大小(HR=2.493,95%CI:1.310~4.742,P<0.01)可作为HCC患者预后评估的独立危险因素。结论:HHLA2表达与HCC患者预后显著相关,是HCC免疫治疗的潜在新靶点。
基金This work was supported by the CAMS Innovation Fund for Medical Sciences(No.2017-I2M-1-005,2016-I2M-1-001)the National Key R&D Program of China(No.2016YFC1303201)+2 种基金the National Natural Science Foundation of China(No.81802299,81502514)the Fundamental Research Funds for the Central Universities(No.3332018070)the National Key Basic Research Development Plan(No.2018YFC1312105).
文摘Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma(ESCC)have shown promising results.However,a comprehensive understanding of B7-CD28 family members in ESCC is still limited.This study aimed to construct a novel B7-CD28 family-based prognosis system to predict survival in patients with ESCC.We collected 179 cases from our previously published microarray data and 86 cases with qPCR data.Specifically,119 microarray data(GSE53624)were used as a training set,whereas the remaining 60 microarray data(GSE53622),all 179 microarray data(GSE53625)and an independent cohort with 86 qPCR data were used for validation.The underlying mechanism and immune landscape of the system were also explored using bioinformatics and immunofluorescence.We examined 13 well-defined B7-CD28 family members and identified 2 genes(ICSOLG and HHLA2)with the greatest prognostic value.A system based on the combination HHLA2 and ICOSLG(B7-CD28 signature)was constructed to distinguish patients as high-or low-risk of an unfavorable outcome,which was further confirmed as an independent prognostic factor.As expected,the signature was well validated in the entire cohort and in the independent cohort,as well as in different clinical subgroups.The signature was found to be closely related to immune-specific biological processes and pathways.Additionally,high-risk group samples demonstrated high infiltration of Tregs and fibroblasts and distinctive immune checkpoint panels.Collectively,we built the first,practical B7-CD28 signature for ESCC that could independently identify high-risk patients.Such information may help inform immunotherapy-based treatment decisions for patients with ESCC.
文摘系统评价人内源性逆转录病毒-H长末端重复关联蛋2(HHLA2)表达与肿瘤预后的关系。方法:计算机检索中国知网(CNKI)、万方、维普、中国生物医学文献数据库、Cochrane Library、Web of Science、PubMed及Embase数据库,纳入公开发表的有关HHLA2表达与肿瘤预后相关性的文献,检索时限均为建库至2020年10月。由2位评价员独立筛选文献、提取资料并评价纳入研究的质量后,采用Stata12.0软件对符合条件的文献进行Meta分析。结果:共纳入11篇文献,包含1671例肿瘤病人。Meta分析结果显示,HHLA2高表达发生死亡的风险是 HHLA2低表达的1.63倍,差异有统计学意义(HR=1.63,95%CI:1.21~2.18,P=0.001)。亚组分析显示,在呼吸道肿瘤和消化道肿瘤HHLA2高表达与总生存期(OS,第一次出现,用英文全称)显著相关(HR=3.02,95%CI:1.54~5.94,P<0.01;HR=1.54,95%CI:1.02~2.31,P<0.05),在泌尿道肿瘤HHLA2高表达与OS无相关性(HR=1.30,95%CI:0.44~3.84,P>0.05)。敏感性分析显示结果稳定,纳入文献无明显发表偏倚(补充统计量值,P>0.05)。结论:HHLA2高表达与消化道和呼吸道肿瘤预后相关,与其他种类的肿瘤预后无关。但由于纳入研究的文献数量有限,该研究结果仍有待于纳入更多的研究观察和证实。
