Although circulating tumor cells (CTCs) have shown promise as potential biomarkers for diagnostic and prognostic assessment in gastric cancer (GC), determining the predictive and prognostic value of programmed death-ligand 1 (PD-L1)-positive CTCs in patients with GC is a challenge. Here, we identified that the expression of total vimentin (VIM) protein was positively correlated with PD-L1 and inhibited CD8+ T-cell activation in patients with GC according to bioinformatics analysis. Notably, coexpression of PD-L1 and cell-surface VIM (CSV) was detected by immunofluorescence and immunohistochemistry assay in locally advanced GC tumor specimens and metastatic lymph nodes. Likewise, CSV expression level was significantly decreased after transiently knocking down PD-L1 in GC cell lines. Based on our established CTC detection platform, CTCs were isolated from peripheral blood samples collected from 70 patients (38 resectable and 32 unresectable) with GC using magnetic positive selection and a CSV-specific monoclonal antibody, 84-1. CSV+ PD-L1+ CTCs were observed in 50 of 70 (71%) GC patient samples, ranging from 0 to 261 mL-1 . A higher number of CSV+ PD-L1+ CTCs were significantly associated with a short survival duration and poor therapeutic response. This study demonstrated that detection of PD-L1+ CTCs using a CSV-enrichment method has promising value as a clinically relevant prognostic marker for GC.

中文翻译：

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PD-L1表达在胃癌患者细胞表面波形蛋白阳性循环肿瘤细胞中的预后意义。

尽管循环肿瘤细胞（CTC）已显示出有望成为胃癌（GC）诊断和预后评估的潜在生物标志物，但确定GC患者程序性死亡配体1（PD-L1）阳性CTC的预测和预后价值仍是一个挑战。在这里，我们根据生物信息学分析确定，GC患者中总波形蛋白（VIM）蛋白的表达与PD-L1正相关，并抑制了CD8 + T细胞活化。值得注意的是，PD-L1和细胞表面VIM（CSV）的共表达是通过免疫荧光和免疫组织化学方法在局部晚期GC肿瘤标本和转移性淋巴结中检测到的。同样，瞬时敲低GC细胞系中的PD-L1后，CSV表达水平显着降低。基于我们已建立的CTC检测平台，使用磁性阳性选择和CSV特异性单克隆抗体84-1，从使用GC收集的70例患者（38例可切除和32例不可切除）的外周血样本中分离出CTC。在70个（71％）GC患者样品中的50个中观察到CSV + PD-L1 + CTC，范围为0至261 mL-1。较高数量的CSV + PD-L1 + CTC与存活时间短和治疗反应差有关。这项研究表明，使用CSV富集方法检测PD-L1 + CTC作为临床相关的GC预后标志物具有广阔的价值。较高数量的CSV + PD-L1 + CTC与存活时间短和治疗反应差有关。这项研究表明，使用CSV富集方法检测PD-L1 + CTC作为临床相关的GC预后标志物具有广阔的价值。较高数量的CSV + PD-L1 + CTC与存活时间短和治疗反应差有关。这项研究表明，使用CSV富集方法检测PD-L1 + CTC作为临床相关的GC预后标志物具有广阔的价值。