HMOX1: A pivotal regulator of prognosis and immune dynamics in ovarian cancer

Abstract

Background

This study investigates the intricate role of Heme Oxygenase 1 (HMOX1) in ovarian cancer, emphasizing its prognostic significance, influence on immune cell infiltration, and impact on the malignant characteristics of primary ovarian cancer cells.

Materials and methods

Our research began with an analysis of HMOX1 expression and its prognostic implications using data from The Cancer Genome Atlas (TCGA) dataset, supported by immunohistochemical staining. Further analyses encompassed co-expression studies, Gene Ontology (GO) annotations, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. We utilized the TIMER and TISIDB platforms to evaluate the immunotherapeutic potential of HMOX1. Additionally, in vitro studies that involved modulating HMOX1 levels in primary ovarian cancer cells were conducted to confirm its biological functions.

Results

Our findings indicate a significant overexpression of HMOX1 in ovarian cancer, which correlates with increased tumor malignancy and poorer prognosis. HMOX1 was shown to significantly modulate the infiltration of immune cells, particularly neutrophils and macrophages. Single-cell RNA sequencing (scRNA-seq) analysis revealed that HMOX1 is predominantly expressed in tumor-associated macrophages (TAMs), with a positive correlation to chemokines and their receptors. An increase in HMOX1 levels was associated with heightened levels of immunoinhibitors, immunostimulators, and MHC molecules. Functional assays demonstrated that HMOX1 knockdown promotes apoptosis, attenuating cell proliferation and invasion, while its overexpression yields opposing effects.

Conclusion

HMOX1 emerges as a critical therapeutic target, intricately involved in immunomodulation, prognosis, and the malignant behavior of ovarian cancer. This highlights HMOX1 as a potential biomarker and therapeutic target in the fight against ovarian cancer.