The exosome plays important roles in driving tumor metastasis, while the role of exosome proteins during organ-specific metastasis in gastric cancer has not been fully understood. To address this question, peripheral blood samples from 12 AGC patients with organ-specific metastasis, including distant lymphatic, hepatic and peritoneal metastasis, were collected to purify exosomes and to detect exosome proteins by Nano-HPLC–MS/MS. Gastric cancer cell lines were used for in vitro experiments. Peripheral blood sample and ascites sample from one patient were further analyzed by single-cell RNA sequencing. GO and KEGG enrichment analysis showed different expression proteins of hepatic metastasis were correlated with lipid metabolism. For peritoneal metastasis, actin cytoskeleton regulation and glycolysis/gluconeogenesis could be enriched. ILK1 and CD14 were correlated with hepatic and peritoneal metastasis, respectively. Overexpression of CD14 and ILK1 impacted the colony formation ability of gastric cancer and increased expression of Vimentin. CD14 derived from immune cells in malignant ascites correlated with high activation of chemokine- and cytokine-mediated signaling pathways. In summary, biological functions of plasma exosome proteins among AGC patients with different metastatic modes were distinct, in which ILK1 and CD14 were correlated with organ-specific metastasis.
外泌体在推动肿瘤转移中发挥着重要作用，然而，在胃癌中，外泌体蛋白在器官特异性转移中的作用尚未被完全理解。为了回答这一问题，从12例具有器官特异性转移（包括远处淋巴转移、肝转移和腹膜转移）的进展期胃癌（AGC）患者中收集外周血样本，以纯化外泌体并利用纳米高效液相色谱-串联质谱（Nano-HPLC–MS/MS）检测外泌体蛋白。使用胃癌细胞系进行体外实验。从一名患者的外周血样本和腹水样本中进一步通过单细胞RNA测序进行分析。基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析显示，与肝转移相关的不同表达蛋白与脂质代谢相关。对于腹膜转移，肌动蛋白细胞骨架调控和糖酵解/糖异生途径可被富集。ILK1和CD14分别与肝转移和腹膜转移相关。CD14和ILK1的过表达影响胃癌的集落形成能力，并增加波形蛋白的表达。源自恶性腹水中免疫细胞的CD14与趋化因子和细胞因子介导信号通路的高激活相关。总之，具有不同转移模式的进展期胃癌患者血浆外泌体蛋白的生物学功能存在差异，其中ILK1和CD14与器官特异性转移相关。
肿瘤(癌症)患者之家