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Effects of HOX family regulator-mediated modification patterns and immunity characteristics on tumor-associated cell type in endometrial cancer

Authors :
JiaoLin Yang
JinPeng Li
SuFen Li
YuTong Yang
HuanCheng Su
HongRui Guo
Jing Lei
YaLin Wang
KaiTing Wen
Xia Li
SanYuan Zhang
Zhe Wang
Source :
Molecular Biomedicine, Vol 5, Iss 1, Pp 1-24 (2024)
Publication Year :
2024
Publisher :
Springer, 2024.

Abstract

Abstract Endometrial cancer (UCEC) is one of three major malignant tumors in women. The HOX gene regulates tumor development. However, the potential roles of HOX in the expression mechanism of multiple cell types and in the development and progression of tumor microenvironment (TME) cell infiltration in UCEC remain unknown. In this study, we utilized both the The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database to analyze transcriptome data of 529 patients with UCEC based on 39 HOX genes, combing clinical information, we discovered HOX gene were a pivotal factor in the development and progression of UCEC and in the formation of TME diversity and complexity. Here, a new scoring system was developed to quantify individual HOX patterns in UCEC. Our study found that patients in the low HOX score group had abundant anti-tumor immune cell infiltration, good tumor differentiation, and better prognoses. In contrast, a high HOX score was associated with blockade of immune checkpoints, which enhances the response to immunotherapy. The Real-Time quantitative PCR (RT-qPCR) and Immunohistochemistry (IHC) exhibited a higher expression of the HOX gene in the tumor patients. We revealed that the significant upregulation of the HOX gene in the epithelial cells can activate signaling pathway associated with tumour invasion and metastasis through single-cell RNA sequencing (scRNA-seq), such as nucleotide metabolic proce and so on. Finally, a risk prognostic model established by the positive relationship between HOX scores and cancer-associated fibroblasts (CAFs) can predict the prognosis of individual patients by scRNA-seq and transcriptome data sets. In sum, HOX gene may serve as a potential biomarker for the diagnosis and prediction of UCEC and to develop more effective therapeutic strategies.

Details

Language :
English
ISSN :
26628651
Volume :
5
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Molecular Biomedicine
Publication Type :
Academic Journal
Accession number :
edsdoj.bb78266384549799ffc3e6b8a8bf333
Document Type :
article
Full Text :
https://doi.org/10.1186/s43556-024-00196-w