Cargando…
Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma
Background: B7-H3, also known as CD276, an important immune checkpoint member of the B7-CD28 family, is confirmed as a promising target after PD-L1 in clinical trials. Although the overexpression of B7-H3 has been associated with invasive metastatic potential and poor prognosis in multiple types of...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039293/ https://www.ncbi.nlm.nih.gov/pubmed/35493085 http://dx.doi.org/10.3389/fcell.2022.819236 |
_version_ | 1784694094902067200 |
---|---|
author | Zhao, Bohui Huang, Zehao Zhu, Xinyi Cai, Huizhu Huang, Yingcheng Zhang, Xiwei Zhang, Zongmin Lu, Haizhen An, Changming Niu, Lijuan Li, Zhengjiang |
author_facet | Zhao, Bohui Huang, Zehao Zhu, Xinyi Cai, Huizhu Huang, Yingcheng Zhang, Xiwei Zhang, Zongmin Lu, Haizhen An, Changming Niu, Lijuan Li, Zhengjiang |
author_sort | Zhao, Bohui |
collection | PubMed |
description | Background: B7-H3, also known as CD276, an important immune checkpoint member of the B7-CD28 family, is confirmed as a promising target after PD-L1 in clinical trials. Although the overexpression of B7-H3 has been associated with invasive metastatic potential and poor prognosis in multiple types of cancer, nothing is known regarding the expression profiles of B7-H3 in papillary thyroid carcinoma (PTC). In this study, we carried out a large-scale analysis of B7-H3 expression in PTC patients and evaluated the potential clinical significance of B7-H3. Methods: In total, data from 1,210 samples, including 867 cases from TCGA and four GEO datasets, were collected for B7-H3–related transcriptome analyses, and 343 postoperative, whole-tumor sections were collected from patients with PTC at our institute for B7-H3–specific immunohistochemistry (IHC) staining. The statistical analysis was primarily accomplished using the R project for statistical computing. Results: B7-H3 positivity was found in 84.8% of PTC patients (291/343), and the mRNA and protein expression levels of B7-H3 in PTC were markedly higher than those of para-tumor tissues (p < 0.001), demonstrating that B7-H3 can serve as a potential diagnostic biomarker for PTC. The significant upregulation of B7-H3 in PTC is caused by distinct patterns of CNVs and CpG DNA methylation. Functional enrichment analysis confirmed that high B7-H3 expression was significantly associated with specific immune features and angiogenesis. High B7-H3 protein expression was associated with tumor size (p = 0.022), extrathyroidal extension (ETE) (p = 0.003), and lymph node metastasis (LNM) (p < 0.001). More importantly, multivariate analysis confirmed that B7-H3 was an independent predictor of relapse-free survival (RFS) (p < 0.05). In the subgroup analysis, positive B7-H3 staining was associated with worse RFS in patients with primary tumor size ≥2 cm (p < 0.05), age ≥55 years (p < 0.05), LNM (p = 0.07), multifocality (p < 0.05), and ETE (p < 0.05). In addition, Circos plots indicated that B7-H3 was significantly associated with other immune checkpoints in the B7-CD28 family. Conclusion: This is the first comprehensive study to elucidate the expression profile of B7-H3 in PTC. Our observations revealed that B7-H3 is a novel independent biomarker for predicting LNM and disease recurrence for PTC patients, and it thus may serve as an indicator that could be used to improve risk-adapted therapeutic strategies and a novel target for immunotherapy strategies for patients who undergo an aggressive disease course. |
format | Online Article Text |
id | pubmed-9039293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90392932022-04-27 Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma Zhao, Bohui Huang, Zehao Zhu, Xinyi Cai, Huizhu Huang, Yingcheng Zhang, Xiwei Zhang, Zongmin Lu, Haizhen An, Changming Niu, Lijuan Li, Zhengjiang Front Cell Dev Biol Cell and Developmental Biology Background: B7-H3, also known as CD276, an important immune checkpoint member of the B7-CD28 family, is confirmed as a promising target after PD-L1 in clinical trials. Although the overexpression of B7-H3 has been associated with invasive metastatic potential and poor prognosis in multiple types of cancer, nothing is known regarding the expression profiles of B7-H3 in papillary thyroid carcinoma (PTC). In this study, we carried out a large-scale analysis of B7-H3 expression in PTC patients and evaluated the potential clinical significance of B7-H3. Methods: In total, data from 1,210 samples, including 867 cases from TCGA and four GEO datasets, were collected for B7-H3–related transcriptome analyses, and 343 postoperative, whole-tumor sections were collected from patients with PTC at our institute for B7-H3–specific immunohistochemistry (IHC) staining. The statistical analysis was primarily accomplished using the R project for statistical computing. Results: B7-H3 positivity was found in 84.8% of PTC patients (291/343), and the mRNA and protein expression levels of B7-H3 in PTC were markedly higher than those of para-tumor tissues (p < 0.001), demonstrating that B7-H3 can serve as a potential diagnostic biomarker for PTC. The significant upregulation of B7-H3 in PTC is caused by distinct patterns of CNVs and CpG DNA methylation. Functional enrichment analysis confirmed that high B7-H3 expression was significantly associated with specific immune features and angiogenesis. High B7-H3 protein expression was associated with tumor size (p = 0.022), extrathyroidal extension (ETE) (p = 0.003), and lymph node metastasis (LNM) (p < 0.001). More importantly, multivariate analysis confirmed that B7-H3 was an independent predictor of relapse-free survival (RFS) (p < 0.05). In the subgroup analysis, positive B7-H3 staining was associated with worse RFS in patients with primary tumor size ≥2 cm (p < 0.05), age ≥55 years (p < 0.05), LNM (p = 0.07), multifocality (p < 0.05), and ETE (p < 0.05). In addition, Circos plots indicated that B7-H3 was significantly associated with other immune checkpoints in the B7-CD28 family. Conclusion: This is the first comprehensive study to elucidate the expression profile of B7-H3 in PTC. Our observations revealed that B7-H3 is a novel independent biomarker for predicting LNM and disease recurrence for PTC patients, and it thus may serve as an indicator that could be used to improve risk-adapted therapeutic strategies and a novel target for immunotherapy strategies for patients who undergo an aggressive disease course. Frontiers Media S.A. 2022-04-12 /pmc/articles/PMC9039293/ /pubmed/35493085 http://dx.doi.org/10.3389/fcell.2022.819236 Text en Copyright © 2022 Zhao, Huang, Zhu, Cai, Huang, Zhang, Zhang, Lu, An, Niu and Li. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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. |
spellingShingle | Cell and Developmental Biology Zhao, Bohui Huang, Zehao Zhu, Xinyi Cai, Huizhu Huang, Yingcheng Zhang, Xiwei Zhang, Zongmin Lu, Haizhen An, Changming Niu, Lijuan Li, Zhengjiang Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma |
title | Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma |
title_full | Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma |
title_fullStr | Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma |
title_full_unstemmed | Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma |
title_short | Clinical Significance of the Expression of Co-Stimulatory Molecule B7-H3 in Papillary Thyroid Carcinoma |
title_sort | clinical significance of the expression of co-stimulatory molecule b7-h3 in papillary thyroid carcinoma |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039293/ https://www.ncbi.nlm.nih.gov/pubmed/35493085 http://dx.doi.org/10.3389/fcell.2022.819236 |
work_keys_str_mv | AT zhaobohui clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT huangzehao clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT zhuxinyi clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT caihuizhu clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT huangyingcheng clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT zhangxiwei clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT zhangzongmin clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT luhaizhen clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT anchangming clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT niulijuan clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma AT lizhengjiang clinicalsignificanceoftheexpressionofcostimulatorymoleculeb7h3inpapillarythyroidcarcinoma |