Spatial transcriptomics reveals prognosis-associated cellular heterogeneity in the papillary thyroid carcinoma...

Area of Science:

• Oncology
• Genomics
• Cell Biology

Background:

• Papillary thyroid carcinoma (PTC) is the most common endocrine tumor, with increasing incidence.
• Tumor microenvironment cellular heterogeneity significantly impacts PTC prognosis.
• Spatial transcriptomics offers a powerful approach to study this heterogeneity.

Purpose of the Study:

• To characterize the spatial distribution and RNA profiles of cells within PTC tissue sections.
• To identify spatial RNA-clinical signatures for prognostic assessment.
• To reveal prognosis-associated cellular heterogeneity in the PTC microenvironment.

Main Methods:

• Spatial transcriptomics combined with pathologist identification.
• Extraction of spatial RNA-clinical signature genes for cell distribution mapping.
• Analysis of cellular heterogeneity using ContourPlot, monocle, trajectory, and ligand-receptor analyses.

Main Results:

• Accurate identification of tumor cells, follicular cells (FCs), atypical follicular cells (AFCs), and immune cells.
• AFCs represent a transitional state between FCs and tumor cells.
• Tumor foci No. 2 and specific ligand-receptor interactions (LAMB3-ITGA2, FN1-ITGA3, FN1-SDC4) correlate with reduced relapse-free survival.

Conclusions:

• Tumor foci No. 2 and identified ligand-receptor interactions are associated with decreased relapse-free survival in PTC.
• These findings suggest potential for improved prognostic strategies and targeted therapies for PTC.
• The developed spatial RNA-clinical analysis method effectively reveals prognostic cellular heterogeneity.