2425 - Single-Cell Atlas and Mechanistic Study of Lung Adenocarcinoma with Pulmonary Sarcomatoid Carcinoma
Presenter(s)
Y. Ma1, J. Yuan1, and D. Chen2; 1Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 2Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
Purpose/Objective(s): To explore the cell heterogeneity of pulmonary sarcomatoid carcinoma(PSC)and the molecular mechanisms of tumor development, and to provide a theoretical basis for the development of more effective diagnostic and therapeutic strategies.
Materials/Methods: In this study, a total of 12 paraffin-embedded and fresh surgical samples from PSC patients and 3 fresh surgical samples from patients with pure LUAD were collected to complete the construction of the single-cell atlas. Integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (ST-seq) were employed for analysis. Through analysis methods such as gene copy number variation, ligand-receptor interaction, transcription factor, and immune checkpoint, the cell subgroups that play a key regulatory role in the mixed tumor were identified. Reverse transcription polymerase chain reaction (RT-PCR), multiplex immunofluorescent staining, and other datasets were used to validate our findings.
Results: A total of 24 distinct cell clusters encompassing 31,546 cells were identified. We found that PSC were more T cells?Neutrophils?Macrophages than LUAD. The fourth group of malignant epithelial cells (MEC4) dominated by PSC were associated with poor prognosis, and the upregulation of genes such as ENO1 may lead to PSCs mutating from LUAD. PSCs had more M2 macrophages and stronger immune responses. The increase of exhausted T cells was regulated by the MIF-CD74 and FN1-CD44 axes, thus producing heterogeneous immune regulation and promoting tumor development. ST-seq analysis revealed that LUAD regulated the CD44 receptor on the surface of PSC through multiple receptors, and the expression of FN1-CD44 was found at the invasive front of the tumor.
Conclusion: M2 macrophages, MEC4, and ENO1 play critical roles in PSC. Targeting these cell subclusters or genes may help improve the severity of PSC, and provides new ideas and directions for developing more effective diagnostic and therapeutic strategies.