目的探究T细胞内抗原1(T-cell intracellular antigen 1,TIA1)在乳腺癌组织中的表达和TIA1启动子区甲基化状态,并分析乳腺癌多层螺旋CT征象与TIA1甲基化状态之间的关系。方法选取2019年2月至2020年3月浙江省台州市第一人民医院收治的50...目的探究T细胞内抗原1(T-cell intracellular antigen 1,TIA1)在乳腺癌组织中的表达和TIA1启动子区甲基化状态,并分析乳腺癌多层螺旋CT征象与TIA1甲基化状态之间的关系。方法选取2019年2月至2020年3月浙江省台州市第一人民医院收治的50例乳腺癌患者,荧光定量PCR法检测所有患者肿瘤组织和癌旁组织TIA1表达水平。通过生物信息学软件MethPrimer预测TIA1启动子区域发现存在cPG岛。采用甲基化特异性聚合酶链反应(Methylmion Specific PCR,MSP)检测肿瘤组织和癌旁组织中TIA1甲基化状态,采用多层螺旋CT对患者进行检查,观察肿块大小、形态、钙化区域、淋巴结转移及边缘,分析TIA1甲基化状态与CT征象之间的相关性。结果乳腺癌组织TIA1表达水平低于癌旁组织(0.50±0.12 vs 0.95±0.10,P=0.00),但TIA1基因启动子甲基化率高于癌旁组织(64% vs 42%,χ2=4.86,P<0.05)。乳腺癌患者TIA1基因启动子甲基化率在肿块形态和有无钙化方面差异无统计学意义(P>0.05)。肿块直径≥2 cm患者TIA1基因启动子甲基化率显著高于肿块直径<2 cm患者(78.57% vs 45.45%,P<0.05),且淋巴结转移患者TIA1基因启动子甲基化率显著高于无淋巴结转移患者(79.17% vs 50.00%,P<0.05)。肿块边缘有毛刺的患者TIA1基因启动子甲基化率显著高于无毛刺的患者(80.77% vs 45.83%,P<0.05)。结论乳腺癌CT显像与TIA1基因启动子甲基化率之间存在相关性,这可为乳腺癌恶变程度和预后的判断提供依据。展开更多
Immunological evasion is one of the defining characteristics of cancers,as the immune modification of an immune checkpoint(IC)confers immune evasion capabilities to tumor cells.Multiple ICs,such as programmed cell dea...Immunological evasion is one of the defining characteristics of cancers,as the immune modification of an immune checkpoint(IC)confers immune evasion capabilities to tumor cells.Multiple ICs,such as programmed cell death protein-1(PD-1)and cytotoxic T-lymphocyte-associated antigen-4(CTLA-4),can bind to their respective receptors and reduce tumor immunity in a variety of ways,including blocking immune cell activation signals.IC blockade(ICB)therapies targeting these checkpoint molecules have demonstrated significant clinical benefits.This is because antibody-based IC inhibitors and a variety of specific small molecule inhibitors can inhibit key oncogenic signaling pathways and induce durable tumor remission in patients with a variety of cancers.Deciphering the roles and regulatory mechanisms of these IC molecules will provide crucial theoretical guidance for clinical treatment.In this review,we summarize the current knowledge on the functional and regulatory mechanisms of these IC molecules at multiple levels,including epigenetic regulation,transcriptional regulation,and post-translational modifications.In addition,we provide a summary of the medications targeting various nodes in the regulatory pathway,and highlight the potential of newly identified IC molecules,focusing on their potential implications for cancer diagnostics and immunotherapy.展开更多
文摘目的探究T细胞内抗原1(T-cell intracellular antigen 1,TIA1)在乳腺癌组织中的表达和TIA1启动子区甲基化状态,并分析乳腺癌多层螺旋CT征象与TIA1甲基化状态之间的关系。方法选取2019年2月至2020年3月浙江省台州市第一人民医院收治的50例乳腺癌患者,荧光定量PCR法检测所有患者肿瘤组织和癌旁组织TIA1表达水平。通过生物信息学软件MethPrimer预测TIA1启动子区域发现存在cPG岛。采用甲基化特异性聚合酶链反应(Methylmion Specific PCR,MSP)检测肿瘤组织和癌旁组织中TIA1甲基化状态,采用多层螺旋CT对患者进行检查,观察肿块大小、形态、钙化区域、淋巴结转移及边缘,分析TIA1甲基化状态与CT征象之间的相关性。结果乳腺癌组织TIA1表达水平低于癌旁组织(0.50±0.12 vs 0.95±0.10,P=0.00),但TIA1基因启动子甲基化率高于癌旁组织(64% vs 42%,χ2=4.86,P<0.05)。乳腺癌患者TIA1基因启动子甲基化率在肿块形态和有无钙化方面差异无统计学意义(P>0.05)。肿块直径≥2 cm患者TIA1基因启动子甲基化率显著高于肿块直径<2 cm患者(78.57% vs 45.45%,P<0.05),且淋巴结转移患者TIA1基因启动子甲基化率显著高于无淋巴结转移患者(79.17% vs 50.00%,P<0.05)。肿块边缘有毛刺的患者TIA1基因启动子甲基化率显著高于无毛刺的患者(80.77% vs 45.83%,P<0.05)。结论乳腺癌CT显像与TIA1基因启动子甲基化率之间存在相关性,这可为乳腺癌恶变程度和预后的判断提供依据。
基金supported by the National Key Research and Development Program of China(No.2021YFC2700903)the National Natural Science Foundation of China(Nos.81672791 and 81872300)+2 种基金the Zhejiang Provincial Natural Science Fund for Distinguished Young Scholars of China(No.LR18C060002)the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LHDMY22H160006)the ZJU-QILU Joint Research Institute and Qilu Group.
文摘Immunological evasion is one of the defining characteristics of cancers,as the immune modification of an immune checkpoint(IC)confers immune evasion capabilities to tumor cells.Multiple ICs,such as programmed cell death protein-1(PD-1)and cytotoxic T-lymphocyte-associated antigen-4(CTLA-4),can bind to their respective receptors and reduce tumor immunity in a variety of ways,including blocking immune cell activation signals.IC blockade(ICB)therapies targeting these checkpoint molecules have demonstrated significant clinical benefits.This is because antibody-based IC inhibitors and a variety of specific small molecule inhibitors can inhibit key oncogenic signaling pathways and induce durable tumor remission in patients with a variety of cancers.Deciphering the roles and regulatory mechanisms of these IC molecules will provide crucial theoretical guidance for clinical treatment.In this review,we summarize the current knowledge on the functional and regulatory mechanisms of these IC molecules at multiple levels,including epigenetic regulation,transcriptional regulation,and post-translational modifications.In addition,we provide a summary of the medications targeting various nodes in the regulatory pathway,and highlight the potential of newly identified IC molecules,focusing on their potential implications for cancer diagnostics and immunotherapy.
