Liaison of Dimethylated arginine between PDL1 and its ligand expressions in Gastric Cancer

Gastric cancer is one of the most common oncological diseases. It can develop in any part of the stomach and spread to other organs, especially in the lungs, liver and oesophagus. Programmed death-1 (PD1), a cell-surface molecule, is involved in a process of dimethylation of arginine and dysregulates the production of nitric oxide in peripheral tissues. Hence, a disruption of the PD1 and PD-L1 axis in patients with severe gastritis. While DDAH activity is normally involved in the processing of neovascularisation, angiogenesis, even in the metastatic phase, the bioavailability of NO and their activity behaviour either interact synergistically or target the PDL1/PD1 activation towards the striking of tumoral activity in patients with gastritis. Therefore, a question naturally arises to understand the dimethylation process of arginine with regards to ADMA and SDMA in conjunction with claudin(s) and involvement of PD-L1 expression and mitochondrial dysregulation in GC.We observed abnormal production of NO levels and reduction of mitochondrial DNA copy numbers in GC patients. Significantly decreased levels of ADMA and excessive influx of arginase activity were assessed in GC patients. PD-L1 expression was significantly higher in GC patients, while suboptimal expression of PD-L1 is in disease control. The abnormal influx of dimethylated arginine and MMP-7 were associated and interlinked with the production of nitric oxide levels. Their association could be with the nitrigenic pathway and possible ways to damage cell surface molecules in GC. Overall, the disruption of the ADMA-SDMA equilibrium fails to maintain the PD1/ PD-L1 axis in GC patients. Therefore, claudin-4, MMP-7, and PD-L1 mRNA overexpression were found in GC, and subsequently, ADMA levels and mitochondrial DNA copy numbers were drastically decreased. Thus, these variables have potential associations to identify novel biomarkers for the diagnosis and therapeutic management of GC.