The advent of rapid and inexpensive sequencing technology allows scientists to decipher intra‐tumor heterogeneity spatially and temporally for resolving the evolutionary history of tumor and the underlying mechanism. However, studies on characterizing heterogeneity of disseminated tumor cells (DTCs) in liquid biopsies are rare because of the rarity and low viability of DTCs as well as a large number of non‐tumor cells. Here, high‐throughput single‐cell transcriptome sequencing technology and rare DTC enrichment method are employed to decipher the heterogeneity and distinct molecular signatures of DTCs in malignant pleural effusion (MPE) from lung adenocarcinoma. Single‐cell transcriptomes of 8213 MPE‐derived cells are acquired for bioinformatics analysis. In these cells from MPE, five main cell populations including tumor, mesothelial, monocyte, T and B cells are identified with specific markers for each group. Tumor cells present in MPE are further divided into four distinct subgroups that are found to be associated with immune response, cell proliferation, apoptosis, and cell adhesion, respectively. Based on the single‐cell dataset of MPE‐derived DTCs, 19 tumor‐specific markers are identified that are also highly expressed at RNA and protein levels in tumor tissues as candidate markers for detection of extraordinarily rare circulating tumor cells in the blood.

中文翻译：

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基于液体活检的单细胞转录组分析表征肺腺癌播散性肿瘤细胞的异质性。

快速且廉价的测序技术的出现使科学家能够在空间和时间上破译肿瘤内的异质性，以解析肿瘤的进化历史和潜在机制。然而，由于 DTCs 的稀有性和低活力以及大量非肿瘤细胞，关于表征液体活检中播散性肿瘤细胞 (DTCs) 异质性的研究很少。在这里，采用高通量单细胞转录组测序技术和罕见的 DTC 富集方法来破译肺腺癌恶性胸腔积液 (MPE) 中 DTC 的异质性和独特的分子特征。获得 8213 个 MPE 衍生细胞的单细胞转录组用于生物信息学分析。在来自 MPE 的这些细胞中，有五种主要细胞群，包括肿瘤、间皮、单核细胞、T 和 B 细胞用每组的特定标记来识别。MPE 中存在的肿瘤细胞进一步分为四个不同的亚组，发现它们分别与免疫反应、细胞增殖、凋亡和细胞粘附有关。基于 MPE 衍生 DTC 的单细胞数据集，确定了 19 种肿瘤特异性标志物，这些标志物也在肿瘤组织中在 RNA 和蛋白质水平高度表达，作为检测血液中极其罕见的循环肿瘤细胞的候选标志物。