9/11/2023 0 Comments Final draft agt![]() Hence, in this study, we conducted a large-scale analysis to identify the clinical risk factors of lipid-metabolism-related genes (LMRGs) for the prediction of the prognosis and responsiveness of chemotherapy in GC, which provides an efficient classification tool for patient stratification in GC. However, the function of AGT in chemotherapy and the underlying mechanism of AGT are poorly understood in the context of GC. In GC, the use of AGT as a prognostic molecule has been issued in previous studies. However, AGT, which is attributed to tumor proliferation and migration, as well as invasion, has been demonstrated to be a diagnostic and prognostic biomarker in colorectal carcinoma. In a transgenic mouse model of hepatocellular carcinoma, the overexpression of human AGT decreased angiogenesis and delayed tumor progression. ![]() AGT with variants was first regarded to be associated with the risk of developing an astrocytoma. Īngiotensinogen (AGT), the precursor substrate of the renin–angiotensin–aldosterone system (RAAS) pathway, has been considered to play a vital role in tumorigenesis. In addition, it has been reported that lipid metabolism is associated with drug resistance when it comes to treating tumor cells. Alterations in the lipid metabolisms of tumor cells have gradually become of concern due to the fact that lipid metabolism is closely associated with tumor development. Moreover, tumor-derived PGE2 also promotes tumor progression by suppressing proliferation and increasing the apoptosis of NK cells. For example, the expression of miR-422a can help to drive a metabolic shift from aerobic glycolysis to oxidative phosphorylation by decreasing pyruvate dehydrogenase kinase 2 (PDK2) and thereby modulate de novo lipogenesis. In GC, lipid metabolism has also been shown to be associated with tumor formation and development. Fatty acids, cholesterol, and phospholipids are the three common lipids that act as energy producers, signaling molecules, and source material for the biogenesis of cell membranes. A dysregulated lipid metabolism represents an important metabolic alteration in the tumor. Lipids constitute the basic structure of biological membranes and function as signaling molecules and an energy source. In this way, predicting the responsiveness of chemotherapy in GC appears to be particularly important. However, chemotherapy, especially neoadjuvant chemotherapy, still plays a vital role in the GC treatment strategy when it comes to refractory GC patients. ![]() At present, molecular classification has huge influences on the medical management of GC, which benefits from the development of next-generation sequencing and other genomic technologies. Despite the decreasing incidence of GC, the prognosis of GC is still unfavorable owing to the frequent presence of stage IV metastatic disease at primary presentation. Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences, is the third most common cause of cancer-related death globally. Our findings suggest that AGT plays a key role in the development of GC, and targeting AGT may help to improve the chemotherapy response of GC patients. The PI3K/AKT pathway agonist 740 Y-P can restore the EMT of GC cells impaired by AGT knockdown and treatment with 5-fluorouracil. Mechanistically, AGT induced significant levels of epithelial–mesenchymal transition (EMT) through the PI3K/AKT pathway. Furthermore, AGT significantly promoted GC growth and migration, and the downregulation of AGT enhanced the chemotherapy response of GC both in vitro and in vivo. The expression of two LMRGs, AGT and ENPP7, can predict the prognosis and response to chemotherapy in GC. The R package “pRRophetic” was applied to calculate the sensitivity of each sample from high- and low-risk groups to chemotherapy drugs. ![]() We further validated this signature prognostic value using the GEO database. Using univariate Cox and LASSO regression analyses, we developed a risk signature based on LMRGs that can distinguish high-GC-risk patients from low-risk patients with significant differences in overall survival. A total of 714 stomach adenocarcinoma patients were enrolled from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. However, the potential values of lipid-metabolism-related genes (LMRGs) concerning prognostic value and the prediction of chemotherapy responsiveness in GC remains unclear. Lipid metabolism has been reported to play an important role in the carcinogenesis and development of GC. Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide, and chemotherapy is still a standard strategy for treating patients with advanced GC. ![]()
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