Single-EV analysis (sEVA) of mutated proteins allows detection of stage 1 pancreatic cancer.

Single-EV analysis (sEVA) of mutated proteins allows detection of stage 1 pancreatic cancer.
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突变蛋白的单ev分析(sEVA)可以检测1期胰腺癌。

DOI:
10.1126/sciadv.abm3453
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发表时间:
2022-04-22
期刊:
影响因子:
13.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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肿瘤细胞衍生的细胞外囊泡(EV)正在被探索作为循环生物标志物,但目前还不清楚批量测量是否可以早期检测癌症。我们假设单EV分析(sEVA)技术可以潜在地提高诊断准确性。使用胰腺癌(PDAC),我们分析了11个模型系中推定的癌症标志物的组成。在KRASmut和/或P53 mut蛋白阳性的亲本PDAC细胞中,仅约40%的EV也是阳性的。在一项涉及16名手术证实的1期PDAC患者的盲法研究中,KRASmut和P53 mut蛋白的检测水平低得多,通常在<0.1%的囊泡中。在16例患者中的15例中,这些囊泡可通过新的sEVA方法检测到。使用建模方法,我们估计目前的PDAC检测极限为~0.1-cm 3肿瘤体积,低于临床成像能力。这些发现确立了sEVA用于早期癌症检测的潜力。使用sEVA方法的人血浆的单囊泡分析允许检测1期胰腺癌。
Tumor cell–derived extracellular vesicles (EVs) are being explored as circulating biomarkers, but it is unclear whether bulk measurements will allow early cancer detection. We hypothesized that a single-EV analysis (sEVA) technique could potentially improve diagnostic accuracy. Using pancreatic cancer (PDAC), we analyzed the composition of putative cancer markers in 11 model lines. In parental PDAC cells positive for KRASmut and/or P53mut proteins, only ~40% of EVs were also positive. In a blinded study involving 16 patients with surgically proven stage 1 PDAC, KRASmut and P53mut protein was detectable at much lower levels, generally in <0.1% of vesicles. These vesicles were detectable by the new sEVA approach in 15 of the 16 patients. Using a modeling approach, we estimate that the current PDAC detection limit is at ~0.1-cm3 tumor volume, below clinical imaging capabilities. These findings establish the potential for sEVA for early cancer detection. Single-vesicle analysis of human plasma with the sEVA method allows detection of stage 1 pancreatic cancers.
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