From Spatial Patterns to Prognosis: Decoding Single-Cell Architecture in Cancer with Hyperplex Immunofluorescence
1Institute of Microbiology and Virology, Riga Stradins University, LV-1067 Riga, Latvia.
Journal of Cancer
|September 17, 2025
Summary
Spatial proteomics using hyperplex imaging and nearest neighbor analysis (NNA) reveals how cell organization impacts cancer prognosis. These methods quantify cell interactions, improving our understanding of tumor microenvironments for better cancer prediction.
Area of Science:
- Spatial biology
- Computational pathology
- Cancer research
Background:
- Cancer prognosis depends on genetic, molecular, and spatial factors within the tumor microenvironment.
- Hyperplex immunofluorescence (IMF) imaging enables high-dimensional, quantitative assessment of cell-cell interactions at the protein level.
- Nearest neighbor analysis (NNA) and proximity analysis are key computational methods for spatial distribution analysis in IMF data.
Purpose of the Study:
- To review the current state of NNA and proximity analysis in cancer research.
- To focus on applications in prognosis using single-cell spatial proteomics data from hyperplex IMF imaging.
- To explore how spatial proteomic signatures can improve prognostic models.
Main Methods:
- Summarizing computational approaches: NNA distance metrics, Ripley's K-function, Voronoi tessellation, and graph-based models.
- Highlighting applications of hyperplex IMF in various cancers.
- Discussing integration of machine learning and AI for predictive modeling using spatial features.
Main Results:
- Spatial proteomic signatures derived from hyperplex IMF imaging and NNA/proximity analysis show promise in improving cancer prognostic models.
- These analyses provide insights into tumor heterogeneity, immune infiltration, and treatment response.
- Integration with AI/ML enhances the predictive power of spatial features.
Conclusions:
- NNA and proximity analysis of hyperplex IMF data offer novel insights into cancer prognosis.
- Addressing challenges in standardization and data quality is crucial for clinical translation.
- This review bridges computational methods and clinical applications for spatial proteomics in cancer.


