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The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma

Background: The PITX gene family, comprising PITX1, PITX2, and PITX3, is critical in organogenesis and has been evolutionary conserved in animals. PITX genes are associated with the advanced progression and poor prognosis of multiple cancers. However, the relationship between the PITX genes and head...

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Autores principales: Zhao, Yaqiong, Zhao, Jie, Zhong, Mengmei, Zhang, Qian, Yan, Fei, Feng, Yunzhi, Guo, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530742/
https://www.ncbi.nlm.nih.gov/pubmed/36204311
http://dx.doi.org/10.3389/fgene.2022.982241
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author Zhao, Yaqiong
Zhao, Jie
Zhong, Mengmei
Zhang, Qian
Yan, Fei
Feng, Yunzhi
Guo, Yue
author_facet Zhao, Yaqiong
Zhao, Jie
Zhong, Mengmei
Zhang, Qian
Yan, Fei
Feng, Yunzhi
Guo, Yue
author_sort Zhao, Yaqiong
collection PubMed
description Background: The PITX gene family, comprising PITX1, PITX2, and PITX3, is critical in organogenesis and has been evolutionary conserved in animals. PITX genes are associated with the advanced progression and poor prognosis of multiple cancers. However, the relationship between the PITX genes and head and neck squamous cell carcinoma (HNSC) has not been reported. Methods: We used data from The Cancer Genome Atlas (TCGA) to analyze the association between PITX mRNA expression and clinicopathological parameters of patients with HNSC. The prognostic value of PITX genes was evaluated using the Kaplan-Meier plotter. Multivariate Cox analysis was used to screen out prognosis-associated genes to identify better prognostic indicators. The potential roles of PITX1 and PITX2 in HNSC prognosis were investigated using the protein-protein interaction (PPI) network, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The correlation between PITX1 and PITX2 expression or methylation and immune cell infiltration was evaluated using the tumor-immune system interaction database (TISIDB). MethSurv was used to identify DNA methylation and its effect on HNSC prognosis. Results: PITX genes expression was correlated with different cancers. PITX1 and PITX2 expression was lower in the patients with HNSC. In HNSC, PITX1 expression was significantly related to the clinical stage, histologic grade, and N stage, while PITX2 expression was only significantly related to the histologic grade. The high expression of PITX3 was significantly related to the histologic grade, T stage, and N stage. Survival analysis revealed that PITX genes had prognostic value in HNSC, which was supported by multivariate Cox analysis. PPI network and enrichment analysis showed that the genes interacting with PITX1 and PITX2 belonged predominantly to signaling pathways associated with DNA binding and transcription. Of the CpG DNA methylation sites in PITX1 and PITX2, 28 and 22 were related to the prognosis of HNSC, respectively. Additionally, PITX1 and PITX2 expression and methylation was associated with tumor-infiltrating lymphocytes (TILs). Conclusion: The PITX genes were differentially expressed in patients with HNSC, highlighting their essential role in DNA methylation and tumor-infiltrating immune cell regulation, as well as overall prognostic value in HNSC.
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spelling pubmed-95307422022-10-05 The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma Zhao, Yaqiong Zhao, Jie Zhong, Mengmei Zhang, Qian Yan, Fei Feng, Yunzhi Guo, Yue Front Genet Genetics Background: The PITX gene family, comprising PITX1, PITX2, and PITX3, is critical in organogenesis and has been evolutionary conserved in animals. PITX genes are associated with the advanced progression and poor prognosis of multiple cancers. However, the relationship between the PITX genes and head and neck squamous cell carcinoma (HNSC) has not been reported. Methods: We used data from The Cancer Genome Atlas (TCGA) to analyze the association between PITX mRNA expression and clinicopathological parameters of patients with HNSC. The prognostic value of PITX genes was evaluated using the Kaplan-Meier plotter. Multivariate Cox analysis was used to screen out prognosis-associated genes to identify better prognostic indicators. The potential roles of PITX1 and PITX2 in HNSC prognosis were investigated using the protein-protein interaction (PPI) network, Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The correlation between PITX1 and PITX2 expression or methylation and immune cell infiltration was evaluated using the tumor-immune system interaction database (TISIDB). MethSurv was used to identify DNA methylation and its effect on HNSC prognosis. Results: PITX genes expression was correlated with different cancers. PITX1 and PITX2 expression was lower in the patients with HNSC. In HNSC, PITX1 expression was significantly related to the clinical stage, histologic grade, and N stage, while PITX2 expression was only significantly related to the histologic grade. The high expression of PITX3 was significantly related to the histologic grade, T stage, and N stage. Survival analysis revealed that PITX genes had prognostic value in HNSC, which was supported by multivariate Cox analysis. PPI network and enrichment analysis showed that the genes interacting with PITX1 and PITX2 belonged predominantly to signaling pathways associated with DNA binding and transcription. Of the CpG DNA methylation sites in PITX1 and PITX2, 28 and 22 were related to the prognosis of HNSC, respectively. Additionally, PITX1 and PITX2 expression and methylation was associated with tumor-infiltrating lymphocytes (TILs). Conclusion: The PITX genes were differentially expressed in patients with HNSC, highlighting their essential role in DNA methylation and tumor-infiltrating immune cell regulation, as well as overall prognostic value in HNSC. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9530742/ /pubmed/36204311 http://dx.doi.org/10.3389/fgene.2022.982241 Text en Copyright © 2022 Zhao, Zhao, Zhong, Zhang, Yan, Feng and Guo. 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 Genetics
Zhao, Yaqiong
Zhao, Jie
Zhong, Mengmei
Zhang, Qian
Yan, Fei
Feng, Yunzhi
Guo, Yue
The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma
title The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma
title_full The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma
title_fullStr The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma
title_full_unstemmed The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma
title_short The expression and methylation of PITX genes is associated with the prognosis of head and neck squamous cell carcinoma
title_sort expression and methylation of pitx genes is associated with the prognosis of head and neck squamous cell carcinoma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530742/
https://www.ncbi.nlm.nih.gov/pubmed/36204311
http://dx.doi.org/10.3389/fgene.2022.982241
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