Single-cell RNA sequencing for the identification of early-stage lung cancer biomarkers from circulating blood

Jinhong Kim; Zhaolin Xu; Paola A Marignani

doi:10.1038/s41525-021-00248-y

Single-cell RNA sequencing for the identification of early-stage lung cancer biomarkers from circulating blood

NPJ Genom Med. 2021 Oct 15;6(1):87. doi: 10.1038/s41525-021-00248-y.

Authors

Jinhong Kim¹, Zhaolin Xu², Paola A Marignani^{3

4}

Affiliations

¹ Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Room 9F1, 5850 College Street, Halifax, Nova Scotia, B3H1X5, Canada.
² Department of Pathology, Faculty of Medicine, Dalhousie University, Room 734C, 5788 University Avenue, Halifax, Nova Scotia, B3H1V8, Canada.
³ Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, Room 9F1, 5850 College Street, Halifax, Nova Scotia, B3H1X5, Canada. paola.marignani@dal.ca.
⁴ Department of Pathology, Faculty of Medicine, Dalhousie University, Room 734C, 5788 University Avenue, Halifax, Nova Scotia, B3H1V8, Canada. paola.marignani@dal.ca.

Abstract

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.