Discovering cancer stem-like cells using Spatial transcriptomic analysis: Nuclear factor I X as a novel therapeutic target for gastric cancer

ABSTRACT Background Gastric cancer (GC) is characterized by significant intratumoral heterogeneity and stem cells presenting as promising therapeutic targets. Despite advancements in spatial transcriptome analysis, unexplored targets for addressing cancer stemness remain unknown. This study aims to identify Nuclear Factor IX (NFIX) as a critical regulator of cancer stemness in GC and evaluate its clinicopathological significance and function. Methods Spatial transcriptome analysis was conducted on GC. NFIX expression’s correlation with clinicopathological factors and prognosis was assessed through immunostaining in 127 GC cases. Functional analyses in cancer cell lines validated these findings. Results Spatial transcriptome analysis stratified GC tissues based on genetic profiles, pinpointing CSC-like cells and further refined the classification to identify and highlight the NFIX’s significance, validated by Monocle 3 and CytoTRACE analyses. Knockdown experiments in cancer cell lines demonstrated the involvement of NFIX in cancer cell proliferation and kinase activity. Conclusions This study underscores spatial transcriptome analysis’s role in refining GC tissue classification and identifying therapeutic targets, highlighting NFIX as pivotal. NFIX expression correlates with poor prognosis and drives GC progression, suggesting its potential as a novel therapeutic target for personalized GC therapies.