The role of LEFTY1 in colorectal liver metastasis

[Objectives] To investigate the expression characteristics and role of left-right determination factor 1 (LEFTY1) in colorectal cancer liver metastasis (CRLM). [Methods] Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data from patients with colorectal cancer (CRC) and CRLM were integrated and analyzed. The regulatory mechanisms of LEFTY1 in the biological functions of tumor cells during CRLM were explored via multi-omics approaches. The expression characteristics and functional role of LEFTY1 in CRC and liver metastasis were further validated using clinical samples and in vitro cell experiments. [Results] In the CRLM cohort of the GSE159216 dataset, the LEFTY1 high-expression group showed significant positive correlations with multiple pro-oncogenic pathways. In the CRC cohort, the LEFTY1 high-expression group was enriched in tumor-suppressive pathways and associated with a better prognosis. In the GSE178318 dataset, the LEFTY1+ epithelial cell subpopulation exhibited higher tumor stemness and malignant characteristics. Immu-nohistochemistry and survival analysis revealed that LEFTY1 expression was significantly higher in CRLM tissues compared to primary CRC tissues and was associated with poor prognosis. In vitro experiments demonstrated that knockdown of LEFTY1 promoted CRC cell growth, proliferation, and migration, while overexpression of LEFTY1 suppressed these malignant phenotypes. [Conclusion] LEFTY1 exhibits distinct roles at different stages of CRC and is a key regulator promoting the progression of CRLM.