Single-cell analysis of distinct cell ecosystems in multiple primary lung adenocarcinoma versus single primary lung adenocarcinoma

Multiple primary lung cancer (MPLC) has been on the rise in recent years, posing significant challenges for diagnosis and treatment. Evidence indicates similarities in survival outcomes between MPLC and single primary lung cancer (SPLC). Here, we performed single-cell RNA sequencing on 15 tumor samples from five patients with MPLC and five with SPLC, including two anatomically distinct nodules from each MPLC patient and one tumor from each SPLC patient. PBMC samples were obtained from seven of these patients, including three with MPLC and four with SPLC. After quality control, 394,928 single-cell profiles were retained for analysis. The transcriptomic features of malignancy in cancer cells were similar between MPLC and SPLC which shared comparable histology. However, distinct tumor microenvironments were found between the groups. In summary, upregulation of macrophage/fibroblasts derived ECM remodeling, enrichment of myeloid derived suppressor cells (MDSC), and deactivation of T and NK cells were found in MPLC. The data also emphasized fibroblasts_POSTN (Fib_POSTN), macrophage_CHIT1 (Mac_CHIT1), and monocytes_CCL20 (Mono_CCL20) as MPLC-enriched populations and depicted their communication networks, highlighting potential therapeutic targets. The results present a single-cell-resolution comparison between MPLC and SPLC.