Pyroptosis-Related Genes May Have a Prominent Role in Uterine Cancer


The linguistic origin of pyroptosis is Greek—pyro meaning fire and ptosis meaning falling or dropped. In science, the term pyroptosis appropriately refers to a highly inflammatory pathway toward regulated cell death. It distinguishes itself from other forms of cellular death with a specific molecular style. Pyroptosis was initially thought to have evolved as a defense against invading intracellular pathogens, but recently other activities have been linked to this cellular process.

 

Pyroptosis Dual Role

Evidence shows that pyroptosis plays a key role in the occurrence, development, and prognosis of uterine corpus endometrial carcinoma (UCEC), one of the most common gynecological tumors, and one that can severely damage a woman’s health. “Pyroptosis is thought to contribute a dual role in tumorigenesis and progression via restraining tumorigenesis and progression and creating a microenvironment that feeds the cancer and accelerates its growth,” wrote Xiaoling Huang, MD, and colleagues in Frontiers in Oncology. “However, the value of genes associated with pyroptosis in UCEC patients has not yet been explored.”

Given the possible significance of pyroptosis-related genes with regard to the progress of UCEC, the research team developed a study using data from the Cancer Genome Atlas (TCGA) database focusing on patients with UCEC. Patients with UCEC were then eliminated if overall survival rates (OS) were missing from their file; 549 patients comprised the compiled dataset.

Differentially expressed genes (DEGs) were screened to identify UCEC genes through weighted correlation network analysis (WGCNA). WGCNA was performed on 5,135 DEGs to confirm key modules and genes of UCEC. Of these, 2,707 were upregulated and 2,428 were downregulated.

 

Genes Effecting Prognosis Identified

Forty-seven pyroptosis genes were identified. Twenty-one UCEC key genes and 42 pyroptosis-related genes that had a confirmed function in UCEC development and progression were also identified. Protein-protein interaction (PPI) and correlation analysis demonstrated a clear relationship between these genes. Pyroptosis-related genes with prognostic properties were identified using Cox regression analysis. It was shown that 11 pyroptosis-related genes correlated with OS. The expression of PYCARD, TIRAP, IRF2 may significantly participate in the progression of UCEC and may become prominent biomarkers or targeted areas of therapy in the future.

As other studies have shown, mortality and morbidity rates for UCEC are increasing worldwide. “UCEC patients always have poor survival clinical results, emphasizing the requirement for more credible biomarkers of long-term patient prognosis and therapy,” wrote Dr. Huang and team.



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