Extracellular vesicle tetraspanin-8 level predicts distant metastasis in non-small cell lung cancer after concurrent chemoradiation
Extracellular vesicle tetraspanin-8 level predicts distant metastasis in non-small cell lung cancer after concurrent chemoradiation
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DOI：
10.1126/sciadv.aaz6162
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发表时间：
2020-03-01
期刊：
影响因子：
13.6
通讯作者：
Hu, Tony Y.
中科院分区：
文献类型：
--
作者：
Liu, Yang;Fan, Jia;Hu, Tony Y.
非小细胞肺癌（NSCLC）是最常见的诊断癌症，也是全球癌症死亡的主要原因。超过一半的NSCLC患者在发生远处转移后死亡，因此需要快速、微创的预后生物标志物来降低死亡率。我们使用蛋白质组学来鉴定在非转移性393 P和转移性344 SQ NSCLC细胞系的细胞外囊泡（EV）上差异表达的蛋白质，并发现四跨膜蛋白-8（Tspan 8）选择性地富集在344 SQ EV上。用过表达Tspan 8的EV处理的NSCLC细胞系也表现出增加的基质胶侵袭。III期转移前NSCLC肿瘤患者血清EV上Tspan 8表达升高也与无远处转移生存率降低相关，表明血清EV上Tspan 8水平可能预测未来的转移。这一结果表明，微创血液检测来分析EV表达Tspan 8可能具有潜在的价值，以指导治疗决策与NSCLC患者，值得进一步研究。
Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. More than half of patients with NSCLC die after developing distant metastases, so rapid, minimally invasive prognostic biomarkers are needed to reduce mortality. We used proteomics to identify proteins differentially expressed on extracellular vesicles (EVs) of nonmetastatic 393P and metastatic 344SQ NSCLC cell lines and found that tetraspanin-8 (Tspan8) was selectively enriched on 344SQ EVs. NSCLC cell lines treated with EVs overexpressing Tspan8 also exhibited increased Matrigel invasion. Elevated Tspan8 expression on serum EVs of individuals with stage III premetastatic NSCLC tumors was also associated with reduced distant metastasis-free survival, suggesting that Tspan8 levels on serum EVs may predict future metastasis. This result suggests that a minimally invasive blood test to analyze EV expression of Tspan8 may be of potential value to guide therapeutic decisions for patients with NSCLC and merits further study.