https://orcid.org/0009-0001-4352-9647
Abstract
Introduction
GRHL1 belongs to the family of Grainyhead-like (GRHL). Previous studies have shown that dysregulation of growth and survival pathways is associated with the GRHL family of gene cancers. Immunotherapy with checkpoint inhibitors has changed the treatment paradigm for many tumors, including endometrial cancer (EC). However, the effect of GRHL1 on immunotherapy in EC and its relationship with immune cell infiltration are poorly understood.
Methods
Differential expression of GRHL1 between EC and normal EC tissues was analyzed by searching the TCGA database, and the results were verified utilizing immunohistochemistry analyses. Next, the relationship between GRHL1, CD8+ T cells and tumor microenvironment (TME) was also investigated, and the effect of GRHL1 expression on immunotherapy in EC was evaluated.
Results
According to the findings, EC tissues had elevated expression levels of GRHL1 relative to normal tissues. Patients with EC who expressed GRHL1 at high levels experienced worse overall survival (OS) and Progression-free survival (PFS) than those whose expression was lower. In addition, GRHL1 expression was negatively correlated with CD8+ T cells, and patients with high GRHL1 expression were less effective in receiving immunotherapy.
Conclusion
The expression of GRHL1 was high in EC patients, and high expression of GRHL1 inhibits the proliferation of CD8+ T cells in the tumor microenvironment of EC and affect the efficacy of immunotherapy.
Abbreviations
EC, endometrial cancer; GRHL1, Grainyhead like transcription factor 1; TCGA, The Cancer Genome Atlas; OS, overall survival; GSEA, Gene set enrichment analysis; IHC, Immunohistochemistry; RT, room temperature; DCs, resting dendritic cells; KM, Kaplan-Meier; FDR, false discovery rate; TME, tumor microenvironment; TIME, Tumor immune microenvironment; TMB, tumor mutation burden; ICI, Immune checkpoint inhibitor; ICB, immune checkpoint blockade; MSigDB, Molecular Signatures Database; FDRs, false discovery rates; TIMER, Tumour Immune Estimation Resource; TCIA, The Cancer Immunome Database; IPS, immune phenomenon scores.
Data Sharing Statement
The following online resources were screened based on this study’s analysis of used clinical data: TCGA (https://www.cancer.gov/), TCIA (https://tcia.at/).
Ethics Approval and Informed Consent
The study involving human participants has been reviewed and approved by the First Affiliated Hospital of Bengbu Medical College’s [2021] 143 ethics committee. The Helsinki Declaration, which outlines moral guidelines for medical research with human participants, was followed in conducting the study. Patients/participants signed a consent form to indicate their agreement to be included in the study with each patient providing their informed consent.
Acknowledgments
We thank Bullet Edits Limited for their invaluable assistance with language editing and manuscript proofreading. In addition, we also acknowledge the open databases, including TCGA, and TCIA, for providing the necessary platform and datasets for this research.
Author Contributions
All authors contributed significantly to the research that was published, whether it was in the conceptualization, research design, implementation, data gathering, analysis, and interpretation, or each of these areas separately; participated in the report’s drafting, revision, or detailed evaluation; approved the final version for publishing; decided upon the journal to which the manuscript has been submitted; and accept responsibility for all aspects of the project.
Disclosure
The authors report no conflicts of interest in this work.