Kim Jinhong, Xu Zhaolin, Marignani Paola A
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Room 9F1, 5850 College Street, Halifax, Nova Scotia, B3H1X5, Canada.
Department of Pathology, Faculty of Medicine, Dalhousie University, Room 734C, 5788 University Avenue, Halifax, Nova Scotia, B3H1V8, Canada.
NPJ Genom Med. 2021 Oct 15;6(1):87. doi: 10.1038/s41525-021-00248-y.
Lung cancer accounts for more than half of the new cancers diagnosed world-wide with poor survival rates. Despite the development of chemical, radiological, and immunotherapies, many patients do not benefit from these therapies, as recurrence is common. We performed single-cell RNA-sequencing (scRNA-seq) analysis using Fluidigm C1 systems to characterize human lung cancer transcriptomes at single-cell resolution. Validation of scRNA-seq differentially expressed genes (DEGs) through quantitative real time-polymerase chain reaction (qRT-PCR) found a positive correlation in fold-change values between C-X-C motif chemokine ligand 1 (CXCL1) and 2 (CXCL2) compared with bulk-cell level in 34 primary lung adenocarcinomas (LUADs) from Stage I patients. Furthermore, we discovered an inverse correlation between chemokine mRNAs, miR-532-5p, and miR-1266-3p in early-stage primary LUADs. Specially, miR-532-5p was quantifiable in plasma from the corresponding LUADs. Collectively, we identified markers of early-stage lung cancer that were validated in primary lung tumors and circulating blood.
肺癌占全球新诊断癌症的一半以上，生存率较低。尽管化学疗法、放射疗法和免疫疗法不断发展，但许多患者并未从这些疗法中获益，因为复发很常见。我们使用Fluidigm C1系统进行了单细胞RNA测序（scRNA-seq）分析，以单细胞分辨率表征人类肺癌转录组。通过定量实时聚合酶链反应（qRT-PCR）对scRNA-seq差异表达基因（DEG）进行验证，发现与来自I期患者的34例原发性肺腺癌（LUAD）的整体细胞水平相比，C-X-C基序趋化因子配体1（CXCL1）和2（CXCL2）的倍数变化值呈正相关。此外，我们发现早期原发性LUAD中趋化因子mRNA、miR-532-5p和miR-1266-3p之间呈负相关。特别地，miR-532-5p在相应LUAD的血浆中可定量。总体而言，我们鉴定了在原发性肺肿瘤和循环血液中得到验证的早期肺癌标志物。
