血清细胞外囊泡含有 SPARC 和 LRG1，可作为结直肠癌的生物标志物，且其存在位置与肿瘤原发部位有关。

Serum extracellular vesicles contain SPARC and LRG1 as biomarkers of colon cancer and differ by tumour primary location.

机构信息

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

EBioMedicine. 2019 Dec;50:211-223. doi: 10.1016/j.ebiom.2019.11.003. Epub 2019 Nov 18.

BACKGROUND

Recently, the distinction between left- and right-sided colon cancer (LCC and RCC) has been brought into focus. RCC is associated with an inferior overall survival and progression-free survival. We aimed to perform a detailed analysis of the diversity of extracellular vesicles (EV) between LCC and RCC using quantitative proteomics and to identify for new diagnostic and prognostic biomarkers.

METHODS

We isolated EVs from patients with LCC, RCC and healthy volunteers, and treated colorectal cancer cell line with serum-derived EVs. We then performed a quantitative proteomics analysis of the serum-derived EVs and cell line treated with EVs. Proteomic data are available via ProteomeXchange with the identifiers PXD012283 and PXD012304. In addition, we assessed the performance of EV SPARC and LRG1 as diagnosis and prognosis biomarkers in colon cancer.

FINDINGS

The expression profile of the serum EV proteome in patients with RCC was different from that of patients with LCC. Serum-derived EVs in RCC promoted cellular mobility more significantly than EVs derived from LCC. EV SPARC and LRG1 expression levels demonstrated area under the receiver-operating characteristic curve values of 0.95 and 0.93 for discriminating patients with colon cancer from healthy controls. Moreover, the expression levels of SPARC and LRG1 correlated with tumour sidedness and were predictive of tumour recurrence.

INTERPRETATION

We identified differences in EV protein profiles between LCC and RCC. Serum-derived EVs of RCC may promote metastasis via upregulation of extracellular matrix (ECM)-related proteins, especially SPARC and LRG1, which may serve as diagnosis and prognosis biomarkers in colon cancer.

背景

最近，左、右半结肠癌（LCC 和 RCC）的区别受到了关注。RCC 患者的总体生存率和无进展生存率较低。我们旨在使用定量蛋白质组学对 LCC 和 RCC 之间的细胞外囊泡（EV）多样性进行详细分析，并鉴定新的诊断和预后生物标志物。

方法

我们从 LCC、RCC 患者和健康志愿者中分离 EV，并使用血清衍生的 EV 处理结直肠癌细胞系。然后，我们对血清衍生的 EV 和用 EV 处理的细胞系进行了定量蛋白质组学分析。蛋白质组学数据可通过 ProteomeXchange 获得，标识符为 PXD012283 和 PXD012304。此外，我们评估了 EV SPARC 和 LRG1 作为结肠癌诊断和预后生物标志物的性能。

结果

RCC 患者血清 EV 蛋白质组的表达谱与 LCC 患者不同。RCC 来源的血清 EV 比 LCC 来源的 EV 更显著地促进细胞迁移。EV SPARC 和 LRG1 的表达水平在区分结肠癌患者和健康对照者方面，曲线下面积的Receiver-operating characteristic 值分别为 0.95 和 0.93。此外，SPARC 和 LRG1 的表达水平与肿瘤侧别相关，并可预测肿瘤复发。