Significance of Altered Enzyme Expression as Potent Biomarkers for the Early Diagnosis of Gastric: Bioinformatic and Biochemical Studies

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Babak Ghobari, Gholamreza Dehghan, Maryam Peymani, Amir Nader Emami Razavi

Abstract

Enzymes play a crucial role in cellular processes, influencing both function and metabolism. This study aimed to elucidate the impact of altered enzyme expression in gastric cancer on patient survival rates and the underlying pathways involved. Data from The Cancer Genome Atlas (TCGA) and other relevant sources was utilized to analyze changes in the expression of all known enzymes. Cox regression analysis explored the relationship between enzyme expression and disease prognosis, incorporating clinical data to construct a predictive model for patient survival. A co-expression network was used to identify pathways associated with these enzymes. To validate the findings, samples from gastric cancer patients (GCP) and adjacent normal tissues were analyzed using RT-qPCR. The expression of the 1818 enzyme was notably identified in both cancerous and normal TCGA samples. Among these, 56 enzymes exhibited significant overexpression in cancer samples, while 158 genes showed significant decreases in expression. These findings highlight the substantial changes in enzymes associated with gastric cancer, potentially affecting its development and progression. The research also revealed that upregulated genes were mainly associated with cell proliferation, metastasis, and DNA repair, while downregulated genes were mainly involved in metabolic pathways e.g. xenobiotic metabolism, fatty acid, and glucose metabolism. The study revealed a remarkable correlation between the modified expression of heparan sulfate glucosamine 3-O-Sulfotransferase 2 (HS3ST2), dehydrogenase/reductase member 1 (DHRS1), and phosphodiesterase 4C (PDE4C). These results suggest that these enzymes could be considered important diagnostic and prognostic biomarkers for the early detection of gastric cancer.

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