KEY TAKEAWAYS
- The study aimed to elucidate the role of CAFs in PTC and their impact on LNM risk.
- The results revealed CAF subsets, especially CD36+ myoCAFs, significantly promote lymph node metastasis in PTC.
Papillary thyroid carcinoma (PTC) is a common global malignancy linked to a heightened risk of lymph node metastasis (LNM). The specific function of cancer-associated fibroblasts (CAFs) in PTC progression and metastasis remains poorly understood.
Yixian Wang and the team aimed to investigate the role of CAFs in PTC and their influence on the risk of LNM.
Researchers collected postoperative hematoxylin-eosin (HE) pathological slides from 984 patients with PTC to analyze CAF density at the tumor’s invasive front using QuPath software. They assessed the relationship between CAF density and LNM.
They integrated single-cell RNA sequencing (scRNA-seq) data from the GSE193581 and GSE184362 datasets to analyze CAF infiltration in PTC. A comprehensive suite of in vitro experiments, including EdU labeling, wound scratch assays, Transwell assays, and flow cytometry, was conducted to elucidate the regulatory role of CD36+ CAFs in 2 PTC cell lines, TPC1 and K1.
The results revealed a notable correlation between elevated fibrosis density at the tumor’s invasive front and LNM. Analysis of scRNA-seq data unveiled metastasis-associated myoCAFs characterized by robust intercellular interactions. Additionally, a diagnostic model based on genes associated with metastasis-associated myoCAFs was developed and refined using deep learning techniques.
Furthermore, it was found that the expression of CD36 in CAFs significantly enhances the proliferation, migration, and invasion capabilities of PTC cells, while also inhibiting PTC cell apoptosis.
The study concluded that there is a significant correlation between LNM risk in PTC and high fibrosis density at the tumor’s invasive front, as observed through analysis of postoperative HE pathological slides from a large patient cohort.
Furthermore, integration of scRNA-seq data enabled comprehensive analysis of CAF infiltration in PTC, identifying metastasis-associated myoCAFs characterized by strong intercellular interactions. In vitro experimental findings suggested that CD36+ expression in CAFs contributes to the progression of PTC. These collective results offer crucial insights into the role of CAF subsets in PTC metastasis.
Funding was provided by the National Natural Science Foundation of China.
Source: https://pubmed.ncbi.nlm.nih.gov/38858612/
Wang Y, Li X, Gang Q, et al. (2024). “Pathomics and single-cell analysis of papillary thyroid carcinoma reveal the pro-metastatic influence of cancer-associated fibroblasts.” BMC Cancer. 2024 Jun 10;24(1):710. doi: 10.1186/s12885-024-12459-4. PMID: 38858612.
