ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1638348
Comprehensive analysis of the papillary thyroid carcinoma identifies CSGALNACT1 as a proliferation driver and prognostic biomarker
Provisionally accepted
- People's Hospital of Qianxinan Prefecture, Guizhou, China
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Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer, yet its cellular heterogeneity and prognostic determinants remain poorly defined. Here, we integrate two single-cell RNA sequencing datasets comprising 20 human thyroid samples to construct a high-resolution cellular atlas of PTC. We identify 29 distinct cellular subpopulations and delineate their composition, dynamics, and interactions in healthy versus tumor tissues. Notably, epithelial and monocyte populations were markedly expanded in PTC, whereas adaptive immune subsets such as B and T cells were diminished. Cell–cell communication analysis revealed enhanced intercellular signaling in the tumor microenvironment, with epithelial and endothelial cells receiving the strongest inputs. Among monocyte-specific transcriptional signatures, we identified 65 prognostic genes via univariate Cox analysis. A LASSO-derived 14-gene risk score robustly stratified patient outcomes, with CSGALNACT1 emerging as a key epithelial-specific, independent prognostic gene. Pseudotime analysis further supported its role in epithelial cell differentiation. Functional validation demonstrated that CSGALNACT1 promotes proliferation in PTC cell lines, suggesting a potential oncogenic function. Immune deconvolution across risk groups revealed substantial divergence in innate and adaptive immune infiltration, indicating a close interplay between tumor-intrinsic transcriptional programs and immune microenvironment remodeling. Collectively, our study provides a comprehensive single-cell framework for PTC, identifies a clinically relevant risk model, and highlights CSGALNACT1 as a potential therapeutic target.
Keywords: Papillary thyroid carcinoma, ScRNA-seq, Bulk RNA-seq, Immune infiltration, Cell Proliferation
Received: 30 May 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Zhao, Zhang, Yao and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Linna Yu, People's Hospital of Qianxinan Prefecture, Guizhou, China
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