Single-cell and whole-transcriptome sequencing of lymph node metastasis-related gene signature: A large-scale pan-cancer cohort, machine learning and experimental study.

BACKGROUND: Lymph node metastasis (LNM) is an independent prognostic factor in numerous types of cancer. Therefore, a LNM-related gene-based nomogram may precisely predict survival and drug sensitivity, and reveal the mechanism underlying LNM. MATERIALS AND METHODS: Gene sequencing profiles of pan-cancer data (33 cancer types) were acquired from The Cancer Genome Atlas UCSC Xena database. Patients were classified into primary (N = 10,071) and testing (N = 5,036) cohorts. The lymph node score (LNscore) was established via single-cell RNA sequencing, whole-transcriptome sequencing, machine learning, and Cox regression analyses. A novel prognosis model, formulated by incorporating the LNscore and clinical characteristics, was evaluated using the concordance index, calibration curve, and decision curve analysis. Moreover, patients were assigned into high- and low-risk groups according to the median LNscore. We investigated these two groups for survival prognosis, functional enrichment, immune infiltration, and drug sensitivity. In addition, we silenced and overexpressed insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2). We also analyzed the behavior of breast cancer (BRCA) cells regarding lymphatic metastasis and lymphangiogenesis in vitro. IGF2BP2 stimulated the proliferation of BRCA cells via 5-Ethynyl-2'-deoxyuridine and Cell Counting Kit-8 experiments. RESULTS: A LNM-related set of 12 genes was identified and utilized to determine the LNscore. The concordance-index of both cohorts in the LNscore-based model was >0.7. The immune landscape revealed that the sensitivity to immunotherapy might be better in the high-risk group versus the low-risk group. In addition, we discovered that IGF2BP2 was overexpressed in BRCA tissues and significantly associated with poor survival. Functional analysis indicated that IGF2BP2 promoted BRCA cell migration and proliferation. Additionally, IGF2BP2 accelerated lymphatic metastasis and lymphangiogenesis in vivo. CONCLUSIONS: A novel LNscore-based model was established via comprehensive analysis of LNM-related genes. This model can accurately predict patient survival and drug sensitivity, and reveal the mechanism of LNM in the pan-cancer setting.

Anti-tumor effect and mechanisms of Timosaponin AIII across diverse cancer progression.

Timosaponin AIII (TAIII), a steroidal saponin derived from Anemarrhena asphodeloides Bunge, has gained attention for its versatile therapeutic properties. While well-established for its anti-inflammatory, antidepressant, and anticoagulant properties, emerging research highlights its potent anti-tumor capabilities. This review synthesizes recent findings on the intricate mechanisms and diverse functions of TAIII in cancer therapy, elucidating its impact on various tumor cells, encompassing the effects of TAIII on critical aspects of cancer progression, including metastasis, apoptosis, and autophagy. Additionally, the shared features of TAIII-induced anti-tumor activities, the factors contributing to the multifaceted anti-cancer activities of TAIII, and an exploration of the advantages and disadvantages associated with the regulation of multiple anti-tumor pathways by TAIII are discussed. Furthermore, the detailed regulation of signaling pathways is delineated and tailored to specific cancer types, providing a comprehensive overview of the potential development of TAIII as a promising anti-tumor agent.