doi:10.3969/j.issn.1004-583X.2025.12.017

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标志物类型	主要亚型	来源	检测技术	优势	局限性	临床应用方向
细胞游离DNA	cfDNA（其中肿瘤来源部分为ctDNA）	肿瘤细胞坏死/凋亡	NGS、ddPCR、PCR	携带肿瘤突变/甲基化信息，可动态监测	外周血浓度低，受炎症干扰	诊断、预后评估、治疗响应监测
细胞游离RNA	cfRNA（miRNA、lncRNA）	肿瘤细胞分泌	RT-qPCR、NGS	反映基因表达动态，组织特异性高	易降解，需EV保护或特殊保存	诊断、复发预警、治疗分层
EVs	外泌体（30~100 nm）	肿瘤细胞内体途径	超离心、密度梯度离心、质谱	内容物稳定，可通过BBB	分离无标准化protocol，检测成本高	诊断、治疗响应监测、靶向药物载体
微囊泡	微囊泡（0.1~1 μm）	肿瘤细胞膜出芽	流式细胞术、免疫磁珠分选	易分离，蛋白标志物丰富	与其他囊泡区分困难	复发预警、炎症相关监测
CTCs	GBM来源CTCs	肿瘤原发灶脱落	免疫细胞化学、微流控芯片、FISH	携带完整肿瘤基因组，反映侵袭能力	外周血稀有，检测敏感度低	分子分型、转移风险评估
TEPs	TEPs	血小板被肿瘤“教育”	RNA测序、RT-qPCR	RNA稳定性高，易获取	缺乏GBM特异性RNA标志物	诊断、假性进展区分、实时监测

标志物类型	主要亚型	来源	检测技术	优势	局限性	临床应用方向
细胞游离DNA	cfDNA（其中肿瘤来源部分为ctDNA）	肿瘤细胞坏死/凋亡	NGS、ddPCR、PCR	携带肿瘤突变/甲基化信息，可动态监测	外周血浓度低，受炎症干扰	诊断、预后评估、治疗响应监测
细胞游离RNA	cfRNA（miRNA、lncRNA）	肿瘤细胞分泌	RT-qPCR、NGS	反映基因表达动态，组织特异性高	易降解，需EV保护或特殊保存	诊断、复发预警、治疗分层
EVs	外泌体（30~100 nm）	肿瘤细胞内体途径	超离心、密度梯度离心、质谱	内容物稳定，可通过BBB	分离无标准化protocol，检测成本高	诊断、治疗响应监测、靶向药物载体
微囊泡	微囊泡（0.1~1 μm）	肿瘤细胞膜出芽	流式细胞术、免疫磁珠分选	易分离，蛋白标志物丰富	与其他囊泡区分困难	复发预警、炎症相关监测
CTCs	GBM来源CTCs	肿瘤原发灶脱落	免疫细胞化学、微流控芯片、FISH	携带完整肿瘤基因组，反映侵袭能力	外周血稀有，检测敏感度低	分子分型、转移风险评估
TEPs	TEPs	血小板被肿瘤“教育”	RNA测序、RT-qPCR	RNA稳定性高，易获取	缺乏GBM特异性RNA标志物	诊断、假性进展区分、实时监测

生物标志物	检测样本	关键发现	检测技术	研究规模（例）
ctDNA（TP53/EGFR）	血浆	55%患者检测到突变，突变阳性者OS缩短3.2个月^[15]	NGS	222
cfDNA浓度	血浆	术前浓度>10 ng/ml者无进展生存期缩短4.5个月，OS缩短6.8个月^[16]	荧光定量法	62
EVs MGMT甲基化	CSF	预测替莫唑胺治疗响应的敏感度85.7%，特异度90%^[30]	ddPCR	49
外泌体miR-19b-3p	血清	诊断GBM的敏感度78%，特异度85%，与肿瘤增殖指数正相关^[29]	RT-qPCR	87
CTCs（GFAP+）	外周血	放疗前检测率72%，放疗后降至8%，CTCs数量>3个/ml者复发风险升高3倍^[37]	荧光报告系统	45
TEPs RNA谱	全血	区分GBM与健康人的准确率95%，区分假性进展与真进展的准确率85%^[43]	RNA测序	120
CSF miR-128/485-3p	CSF	诊断GBM的敏感度82%，特异度91%，可区分WHO Ⅲ级与Ⅳ级胶质瘤^[23]	RT-qPCR	63
微囊泡miR-625-5p	血浆	术后表达降至正常，复发时升高2倍以上，预警复发的敏感度80%^[33]	RT-qPCR	36

生物标志物	检测样本	关键发现	检测技术	研究规模（例）
ctDNA（TP53/EGFR）	血浆	55%患者检测到突变，突变阳性者OS缩短3.2个月^[15]	NGS	222
cfDNA浓度	血浆	术前浓度>10 ng/ml者无进展生存期缩短4.5个月，OS缩短6.8个月^[16]	荧光定量法	62
EVs MGMT甲基化	CSF	预测替莫唑胺治疗响应的敏感度85.7%，特异度90%^[30]	ddPCR	49
外泌体miR-19b-3p	血清	诊断GBM的敏感度78%，特异度85%，与肿瘤增殖指数正相关^[29]	RT-qPCR	87
CTCs（GFAP+）	外周血	放疗前检测率72%，放疗后降至8%，CTCs数量>3个/ml者复发风险升高3倍^[37]	荧光报告系统	45
TEPs RNA谱	全血	区分GBM与健康人的准确率95%，区分假性进展与真进展的准确率85%^[43]	RNA测序	120
CSF miR-128/485-3p	CSF	诊断GBM的敏感度82%，特异度91%，可区分WHO Ⅲ级与Ⅳ级胶质瘤^[23]	RT-qPCR	63
微囊泡miR-625-5p	血浆	术后表达降至正常，复发时升高2倍以上，预警复发的敏感度80%^[33]	RT-qPCR	36

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