Integrated spatial and single-cell transcriptomics identifies TBX2 as a key transcriptional regulator in papillary thyroid carcinoma
Abstract
MethodsThis study integrated and analyzed the spatial transcriptomics and single-cell transcriptomics data of 10 sequencing samples from 9 patients, comprising 9 primary tumor tissues from PTC patients and 1 adjacent non-tumor tissue. A canonical correlation analysis (CCA)-based approach was used for multi-sample integration. Cell types were annotated using the scType framework combined with thyroid-specific marker genes. Highly variable gene (HVG) and spatially variable gene (SVG) were jointly screened to identify candidate key transcription factors. In addition, immunohistochemistry (IHC) was performed on 72 PTC tissue samples and 20 adjacent normal tissues to evaluate TBX2 protein expression and cellular localization. Finally, KTC-1 and TPC-1 PTC cell lines were selected to establish stable TBX2 knockdown models. The biological functions of TBX2 were further evaluated by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), cell counting kit-8 (CCK-8) assays, colony formation assays, and migration and invasion assays.ResultsIntegrated analysis generated a high-resolution cellular atlas of the PTC TME and identified nine major cell populations, including tumor epithelial cells, follicular cells (FC), FC2, endothelial cells, macrophages, T cells, B cells, cancer-associated fibroblasts and activated fibroblast-like cells. Marked inter-sample heterogeneity in cellular composition was observed, although the overall cellular architecture remained relatively conserved. Further joint screening of HVG and SVG identified TBX2 as a potential key regulatory transcription factor. Single-cell analysis showed that TBX2 was highly expressed in tumor-associated stromal cells, particularly cancer-associated fibroblasts, and was significantly upregulated in tumor epithelial cells compared with adjacent follicular cells. IHC staining revealed that TBX2 was predominantly localized in the nucleus of PTC cells. The expression level of TBX2 in PTC tissues was significantly higher than that in adjacent normal tissues (mean IHC score: 7.33 vs 0.95, P<0.000 1). Functional experiments showed that TBX2 knockdown significantly reduced TBX2 mRNA and protein expression in KTC-1 and TPC-1 cells, and significantly suppressed cell proliferation, colony formation, migration and invasion.ConclusionBy integrating spatial transcriptomic and single-cell transcriptomic data, this study systematically delineated the cellular composition and heterogeneity of the PTC TME and identified TBX2 as a potential key transcription factor promoting PTC progression. TBX2 plays an important role in maintaining the malignant biological behavior of PTC cells, suggesting that it may serve as a potential therapeutic target for papillary thyroid carcinoma.Background and purposePapillary thyroid carcinoma (PTC) is the most common type of differentiated thyroid cancer, with its incidence continuing to rise globally in recent years. Although the majority of patients have a relatively favorable prognosis, a subset still experiences local invasion, lymph node metastasis, and resistance to radioactive iodine therapy, which significantly impairs long-term outcomes. The cellular composition and spatial heterogeneity of the tumor microenvironment (TME) play important roles in the initiation and progression of PTC; however, the key regulatory molecules involved remain insufficiently characterized. The integration of single-cell and spatial transcriptomics provides a robust approach to comprehensively dissect the cellular composition and spatial features of the PTC tumor microenvironment. This study aims to systematically elucidate the cellular landscape and spatial heterogeneity of the PTC TME through the integration of these two technologies, and to identify key transcription factors involved in PTC progression, thereby providing a theoretical basis and potential therapeutic targets for the precision diagnosis and treatment of PTC.
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BibTeX
@article{miao2026integrated,
title = {{Integrated spatial and single-cell transcriptomics identifies TBX2 as a key transcriptional regulator in papillary thyroid carcinoma}},
author = {ZHANG Miao and WU Xiaocan and DONG Qiman and ZHENG Xiangqian and RUAN Xianhui},
journal = {Zhongguo aizheng zazhi},
year = {2026},
month = sep,
url = {http://www.china-oncology.com/zh/article/doi/10.19401/j.cnki.1007-3639.2026.09.004/},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Integrated spatial and single-cell transcriptomics identifies TBX2 as a key transcriptional regulator in papillary thyroid carcinoma
AU - ZHANG Miao
AU - WU Xiaocan
AU - DONG Qiman
AU - ZHENG Xiangqian
AU - RUAN Xianhui
PY - 2026
DA - 2026/09/01
JO - Zhongguo aizheng zazhi
UR - http://www.china-oncology.com/zh/article/doi/10.19401/j.cnki.1007-3639.2026.09.004/
AB - MethodsThis study integrated and analyzed the spatial transcriptomics and single-cell transcriptomics data of 10 sequencing samples from 9 patients, comprising 9 primary tumor tissues from PTC patients and 1 adjacent non-tumor tissue. A canonical correlation analysis (CCA)-based approach was used for multi-sample integration. Cell types were annotated using the scType framework combined with thyroid-specific marker genes. Highly variable gene (HVG) and spatially variable gene (SVG) were jointly screened to identify candidate key transcription factors. In addition, immunohistochemistry (IHC) was performed on 72 PTC tissue samples and 20 adjacent normal tissues to evaluate TBX2 protein expression and cellular localization. Finally, KTC-1 and TPC-1 PTC cell lines were selected to establish stable TBX2 knockdown models. The biological functions of TBX2 were further evaluated by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), cell counting kit-8 (CCK-8) assays, colony formation assays, and migration and invasion assays.ResultsIntegrated analysis generated a high-resolution cellular atlas of the PTC TME and identified nine major cell populations, including tumor epithelial cells, follicular cells (FC), FC2, endothelial cells, macrophages, T cells, B cells, cancer-associated fibroblasts and activated fibroblast-like cells. Marked inter-sample heterogeneity in cellular composition was observed, although the overall cellular architecture remained relatively conserved. Further joint screening of HVG and SVG identified TBX2 as a potential key regulatory transcription factor. Single-cell analysis showed that TBX2 was highly expressed in tumor-associated stromal cells, particularly cancer-associated fibroblasts, and was significantly upregulated in tumor epithelial cells compared with adjacent follicular cells. IHC staining revealed that TBX2 was predominantly localized in the nucleus of PTC cells. The expression level of TBX2 in PTC tissues was significantly higher than that in adjacent normal tissues (mean IHC score: 7.33 vs 0.95, P<0.000 1). Functional experiments showed that TBX2 knockdown significantly reduced TBX2 mRNA and protein expression in KTC-1 and TPC-1 cells, and significantly suppressed cell proliferation, colony formation, migration and invasion.ConclusionBy integrating spatial transcriptomic and single-cell transcriptomic data, this study systematically delineated the cellular composition and heterogeneity of the PTC TME and identified TBX2 as a potential key transcription factor promoting PTC progression. TBX2 plays an important role in maintaining the malignant biological behavior of PTC cells, suggesting that it may serve as a potential therapeutic target for papillary thyroid carcinoma.Background and purposePapillary thyroid carcinoma (PTC) is the most common type of differentiated thyroid cancer, with its incidence continuing to rise globally in recent years. Although the majority of patients have a relatively favorable prognosis, a subset still experiences local invasion, lymph node metastasis, and resistance to radioactive iodine therapy, which significantly impairs long-term outcomes. The cellular composition and spatial heterogeneity of the tumor microenvironment (TME) play important roles in the initiation and progression of PTC; however, the key regulatory molecules involved remain insufficiently characterized. The integration of single-cell and spatial transcriptomics provides a robust approach to comprehensively dissect the cellular composition and spatial features of the PTC tumor microenvironment. This study aims to systematically elucidate the cellular landscape and spatial heterogeneity of the PTC TME through the integration of these two technologies, and to identify key transcription factors involved in PTC progression, thereby providing a theoretical basis and potential therapeutic targets for the precision diagnosis and treatment of PTC.
SN - 1007-3639
ER -