Correlation Between Early Gastric Cancer And Gastric Xanthelasma

Aims: To investigate the correlation between early gastric cancer and gastric xanthelasma.Methods: Part I: Clinical characteristics and blood lipid levels of patients with gastric xanthelasma.Patients,who be hospitalized at the Department of Gastroenterology,Second People's Hospital of Wuhu,due to upper gastrointestinal symptoms,were erolled in this study during the period from August 2016 to August 2018.According to the results of endoscopic examination and histopathological findings,469 patients were divided into two groups: patients with gastric xanthelasma were included in the xanthelasma group(n=279);patients with chronic non-atrophic gastritis of gastric macular tumor were normal controls(n=193).The patients' previous medical histories were investigated.The blood lipid levels(plasma triglyceride,total cholesterol,high-density lipoprotein and low-density lipoprotein)were examed.The observed indicators include patient gender,age,clinical diagnosis,endoscopic finding and diagnosis,pathological results,with or without the complications such as hypertension,coronary heart disease,diabetes,cholelithiasis;blood triglyceride,total cholesterol(TC),high-density lipoprotein(HDL)and low-density lipoprotein(LDL)levels;the size,number,and location of xanthelasma in the xanthelasma group;with or without upper gastrointestinal ulcers,polyps,intestinal metaplasia,dysplasia,and gastric cancer.Part II: Comparison of blood tumor marker levels in patients in gastric xanthelasma group and early gastric cancer group A total of 75 patients were enrolled from August 2016 to August 2018 in the Endoscopy Center of Wuhu Second People's Hospital.75 cases were divided into three groups: patients with chronic non-atrophic gastritis(normal control group,n=35),patients with xanthelasma and chronic non-atrophic gastritis(xanthelasma group,n=20)and early gastric cancer patients(EGC group,n=20).All subjects were examined by endoscopy with pathological biopsy of the lesions.The specimens of EGC patients were sent for pathological examination.Blood tumor markers(CEA,CA199,CA125)were tested in all patients.Part III: miRNA sequencing of gastric xanthelasma,gastric cancer and normal gastric mucosa A total of 18 patients were collected from April to May 2018 at the endoscopy center of the Second People's Hospital of Wuhu.The 18 patients(6 patients with EGC,6 patients with gastric xanthelasma and 6 patients with chronic non-atrophic gastritis)were diagnosed by Endoscopic and pathological examination.Fresh biopsy specimens were taken from gastric xanthelasmas,EGCs or the gastric mucosa of chronic non-atrophic gastritis during endoscopy.The specimens were chopped and placed in RNA protection solution.After incubation at 4 °C overnight,stored in a refrigerator at-20 °C and transported with dry ice.RNA extraction and quality inspection,miRNA sequencing and results analysis were all completed by Shanghai Jingneng Biotechnology Co.,Ltd.Samples were subjected to high-throughput sequencing using the single-ended 50 bp sequencing mode of the Illumina Hiseq 3000 sequencing platform.The results were mainly analyzed by original sequencing results,sequence alignment,new miRNA prediction,miRNA differential expression analysis,differential miRNA target gene prediction,differential target gene GO and KEGG functional analysis.Results: In the first part of the study,276 patients with gastric xanthelasma were included,and 193 patients were inrolled in the normal control group.Of the 276 patients with xanthelasma,61.2%(169 cases)were single and 38.8%(107 cases)were multiple.The predilection site of xanthelasma was gastric antrum(59.1%).The gender and age distribution of the patients with xanthelasma and normal control group were significantly higher than those of the normal control group in the xanthelasma group(P=0.009),and the proportion of patients with diabetes was significantly increased(P=0.014).The average blood lipid level of xanthelasma and normal control group was in the normal range.The HDL level of patients with xanthelasma was significantly lower than that of normal control group(P=0.02).There were not significantly differences in the level of TC,LDL between the two groups.Part II: This study included 20 patients with gastric xanthelasma,20 patients with early gastric cancer,and 35 patients with chronic non-atrophic gastritis.The levels of CEA and CA125 in blood increased gradually among the three groups.The CEA levels in the early gastric xanthelasma were significantly higher than in the chronic non-atrophic gastritis group(P=0.012).There was no significant difference between the other groups.The third part included:(1)high-throughput sequencing detection of differential miRNA gastric xanthelasma and gastric cancer group were screened for differentially expressed miRNA 88 species,miRNAs with significantly up-regulated expression in gastric cancer tissues included: hsa-miR-196a-5p,hsa-miR-1246,hsa-miR-552-3p,hsa-miR-483-5p,hsa-miR-106b-3p,etc.,miRNAs with significantly down-regulated expression include hsa-miR-129-2-3p,hsa-miR-211-5p,hsa-miR-577 and so on.A total of 87 differentially expressed miRNAs were screened from the gastric mammography group and the normal control group.The miRNAs with significantly up-regulated expression in the gastric macular tumor tissues included hsa-miR-124-3p and hsa-miR-7-5p,and the expression was significantly up-regulated.miRNAs include hsa-miR-211-5p,hsa-miR-514a-3p,hsa-miR-4709-5p,hsa-miR-3145-3p and the like.(2)GO function annotation results: gastric xanthelasma compared with gastric cancer and normal control group,the molecular biological processes involved in differential genes mainly included: organelle composition,cellular metabolic processes,phosphate compound metabolism,ATP binding,nucleotide binding,catalysis Activity,etc.(3)KEGG signaling pathway enrichment results: Compared with gastric cancer and normal control group,the signal pathways significantly enriched in macular tumor tissue are: glycerophospholipid metabolism,tumor choline metabolism,AMPK signaling pathway,and endocytosis.Conclusions: 1.The serum HDL level of patients with gastric xanthelasma significantly decreased,and the occurrence of macular tumor may be related to the disorder of lipid metabolism;2.Gastric xanthelasma may be associated with the development of gastric cancer and with differential expression of miRNAs,possibly through choline metabolism or AMPK signaling pathways.