Spatial and Single-Cell Transcriptomics Unraveled Spatial Evolution of Papillary Thyroid Cancer

Area of Science:

• Oncology
• Genomics
• Cell Biology

Background:

• Papillary thyroid cancer (PTC) recurrence and metastasis pose significant clinical challenges.
• Current diagnostic methods lack variant-specific morphological criteria and suffer from high signal-to-noise ratios in mutation-based approaches.
• Intratumor heterogeneity, crucial for understanding cancer progression, is often lost in conventional molecular classifications.

Purpose of the Study:

• To integrate single-cell RNA sequencing (scRNA-seq) and spatially-resolved transcriptomics (SRT) for a comprehensive analysis of PTC.
• To elucidate the mechanisms driving spatial heterogeneity, malignancy, and metastasis in PTC by linking transcriptome data with local morphology.
• To develop improved diagnostic strategies for PTC based on single-cell and spatial analyses.

Main Methods:

• Integration of scRNA-seq to capture individual cell transcriptomes.
• Application of SRT to retain spatial information and morphological context.
• Comparative analysis of transcriptomic data with morphological features to understand tumor evolution.
• Identification of molecular footprints associated with malignancy and metastasis.

Main Results:

• PTC cells exhibit diverse evolutionary routes driven by enhanced aerobic metabolism and suppressed protein synthesis.
• Cell-cell interactions play a role in PTC progression.
• Two distinct malignant and metastatic molecular signatures were identified to differentiate PTC cells from normal thyrocytes.
• Resistance to ferroptosis was found to be a contributing factor in PTC evolution.

Conclusions:

• The study advances the understanding of intratumor spatial heterogeneity and evolution in PTC at single-cell and spatial levels.
• The findings provide a foundation for developing more precise diagnostic and prognostic strategies for papillary thyroid cancer.
• Integrating transcriptomic and spatial data offers a powerful approach to dissect complex tumor biology.