In this study, the expression levels of LOX-1 and CD-36 genes, and serum levels of hs-CRP and ox-LDL in our target groups were compared based on gastritis and H. pylori. The serum levels of hs-CRP and ox-LDL were higher in H. pylori-positive patients. Our results indicated that H. pylori increased LOX-1 and decreased CD-36 gene expression. Moreover, a weak correlation was observed between the serum level of CRP and the expression of LOX-1, while there was no correlation between the serum level of ox-LDL and the expression of genes. In summary, our results demonstrated that there were higher serum levels of CRP and ox-LDL and expression of the LOX-1 gene in the group with negative H. pylori-gastritis positive than in the control group. Although in the H. pylori and gastritis-positive group, the serum level of CRP and LOX-1expression was higher, the expression of CD-36 decreased despite the high level of ox-LDL (Fig. 5).
In this work, the effects of smoking, alcohol consumption, use of any drugs, use of antacids, use of anti-inflammatory medications, antibiotics, anti-H. Pylori drugs were excluded according to the inclusion and exclusion criteria. It furthermore balanced the body mass index in the three groups. In addition, none of the people in their first-degree relatives had a history of gastric cancer. Therefore, the effects seen were due to infection with this bacterium and gastritis.
The role of H. pylori, inflammation and hyperlipidemia in the evolution of distal gastric adenocarcinoma has been demonstrated [25–27] ; however, its molecular mechanism is unclear. According to the results of the study conducted by Huang et al., plasma levels of hs-CRP and ox-LDL were higher in atherosclerotic CHD patients with Cag+H. pylori infection . Studies by Jafarzadeh et al. showed that although serum hs-CRP levels increased in H. pylori infection, this increase in hs-CRP was not affected by the bacterial CagA status . In our study, it appears in the H. pylori/ gastritis positive group, H. pylori were the leading cause of the increase in serum hs-CRP levels.
Studies show that in gastric cancer, ox-LDL interaction with the LOX-1 receptor causes NF-κB pathway activation and increases vascular endothelial growth factor C (VEGF-c) expression . Furthermore, the use of ox-LDL binding inhibitor inhibits VEGEF-c expression. Pascual et al. in their study found that CD-36+ metastasis initiating cells in highly invasive melanoma, lung carcinoma, bladder, and breast cancer patients were associated with a poor prognosis. Moreover, Inhibition of CD-36 in animal models of breast cancer and melanoma prevented metastasis .
In study conducted by the Kashihara et al. Investigating noncancerous gastric tissue obtained from 39 gastrectomy patients, the level of glycoprotein thrombospondin 1 (TSP-1), which is a CD-36 ligand, was measured, and patients in both groups with high and low TSP-1 were compared. Noncancerous gastric tissue of patients with high TSP-1 levels had higher carcinogenesis and more active CD-36 signaling. Although in these studies several patients had H. pylori infection, the effect of H. pylori on CD-36 gene expression was not investigated .
Some studies have investigated the effect of palmitic acid fatty acids as CD-36 ligand on signal transduction pathways in gastric cancer metastasis [30, 15]. Accordingly, CD-36 levels show a significant upregulation in malignant tissue. In these studies, they introduced CD-36 as an oncogenic factor involved in cancer progression. However, another study reported downregulation of CD-36 in Cancer-Associated Fibroblasts (CAFs), in more aggressive tumors . Although low levels of CD-36 are associated with low TNM (tumor, node, metastasis) classification in pancreatic ductal adenocarcinoma (PDAC) cancer, they are associated with a larger tumor size and a weaker disease prognosis .
Analysis of the mRNA extracted from gastric tissue samples of 10 patients with H. pylori showed that out of 13817 transcripts, 98 transcripts increased after H. pylori treatment and bacterial eradication (P<0.02 fold change threshold) . CD-36 was one gene whose expression increased significantly (approximately 2.95 times). In agreement with the investigation conducted by Resnick et al., the expression analysis in our study exhibited a decrease in CD-36 expression in the H. pylori group.
According to the results, the primary reason for high LOX-1 expression in the H. pylori group is the activation of the inflammatory pathway. It appears that CRP acts as the dominant ligand for the LOX-1 receptor. There is evidence that CRP is suggested as a ligand for LOX-1 and induced genes involved in tumorigenesis [33, 34]. In addition to the ligands for LOX-1 and CD-36, direct bacterial interaction with these receptors may have caused the molecular changes observed in gastric cells. Kattoor et al. in their study revealed that infectious agents, such as Chlamydia pneumoniae and H. pylori, could increase their expression by direct interaction with the LOX-1 receptor . In this study, they showed that Chlamydia pneumoniae bound to LOX-1 in human umbilical vein endothelial cells (HUVECs) and allowed ox-LDL to enter the cells. They also observed this mechanism in the lung and adductor tissues of mice. However, this study showed that Chlamydia pneumoniae was only useful on LOX-1 and had no effect on the expression and signaling of the CD-36 gene . One limitation of this study was the small amount of biopsy and serum samples of patients; therefore, molecular studies at the protein level were impossible to conduct.