A Pan-Cancer Analysis to Provide Insight into the Immunological Role and Prognostic Value of HTRA3

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• High-temperature requirement factor A3 (HTRA3) is implicated in apoptosis and cancer development.
• The precise regulatory mechanisms of HTRA3 in tumors remain incompletely understood.
• Comprehensive analysis is needed to elucidate HTRA3's role across various cancer types.

Purpose of the Study:

• To conduct a pan-cancer multi-omics analysis of High-temperature requirement factor A3 (HTRA3).
• To investigate the association of HTRA3 with cancer diagnosis, prognosis, and the tumor microenvironment.
• To evaluate HTRA3's potential as a diagnostic and therapeutic biomarker.

Main Methods:

• Utilized multi-omics data from TCGA, cBioPortal, GeneMANIA, DAVID, TIMER2.0, SangerBox, and RNAactDrug.
• Performed analyses including gene expression, survival prognosis, mutation, gene-gene interaction, enrichment, and drug sensitivity.
• Assessed correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoint (ICP) genes, and cancer-associated fibroblasts (CAFs).

Main Results:

• HTRA3 exhibits aberrant expression across diverse cancers, significantly correlating with diagnosis, prognosis, TMB, MSI, ICP genes, and drug sensitivity.
• HTRA3 is implicated in cancer pathways, particularly extracellular matrix (ECM) alterations and epithelial-mesenchymal transition (EMT).
• HTRA3 expression positively correlates with CAFs, endothelial cells, and immune/stromal/ESTIMATE scores within the tumor microenvironment.

Conclusions:

• HTRA3 overexpression is linked to poor prognosis and modulation of the tumor immune response in multiple cancers.
• HTRA3 demonstrates potential as a novel biomarker for cancer diagnosis.
• HTRA3 may serve as a valuable target for cancer treatment strategies.