Objective To map the genome-wide distribution profile of histone H3K27me3 modification in diffuse gastric cancer tissues,identify target genes regulated by H3K27me3,and primarily explore the potential mechanism of its modification reprogramming in the occurrence and development of the tumor.Methods Normal gastric mucosal tissues and diffuse gastric cancer tissues were harvested from the patients who underwent examinations or treatments in the departments of gastroenterology and gastrointestinal surgery of our medical center between 2021 and 2023.There were 14 patients in the normal group(6 males and 8 females,average age of 46 years)and 14 patients in the gastric cancer group(8 males and 6 females,average age of 63 years).Cleavage under target and tagmentation(CUT&Tag)technology was employed to capture genomic regions modified by H3K27me3,and analyze the reprogramming characteristics of these modifications.RNA sequencing data,data from high-throughput chromosome conformation capture(Hi-C)technology,and publicly available single-cell data were integrated to investigate the target genes regulated by the reprogramming of H3K27me3 modifications in diffuse gastric cancer cells.Results The quality of the CUT&Tag and RNA sequencing data met the standards required for subsequent analysis.Histone H3K27me3 modifications in normal gastric mucosa and diffuse gastric cancer tissues were primarily distributed in distal intergenic regions and intronic regions.In gastric cancer tissues,compared to normal tissues,there was significant reprogramming of H3K27me3 modifications,characterized by a marked reduction in overall H3K27me3 signal intensity.The loss of 2 912 H3K27me3 signal peaks might lead to the up-regulation of 822 tumor-associated genes.Among them,56 genes displayed the most significant up-regulation(fold change in signal intensity≥2,P<0.05),with notable enrichment in the mammalian target of rapamycin complex 1(mTORC1)signaling pathway.Specifically,the methionine transporter SLC7A5 and the cystine transporter SLC7A11 were found to have the highest expression levels in gastric cancer tissues.Single-cell data revealed that the abnormal overexpression of SLC7A11 in diffuse gastric cancer was primarily observed in tumor epithelial cells.Further validation using public data and immunohistochemical experiments confirmed the elevated expression of SLC7A11 in diffuse gastric cancer,which is associated with poor prognosis in gastric cancer patients.Conclusion The reprogramming of histone H3K27me3 modification is an important epigenetic characteristic in diffuse gastric cancer.Loss of H3K27me3 signal peaks may up-regulate the expression of SLC7A11 in diffuse gastric cancer cells,and thereby promote tumor progression.

Objective To investigate the diagnostic value of endoscopic sign of light blue crest(LBC)capsuling papillary lesion(LCPL)for high-risk intestinal metaplasia(IM).Methods A total of 314 patients(352 biopsy specimens)who underwent endoscopic examination and biopsy in Department of Gastroenterology of Army Medical Center of PLA from January 2021 to June 2023 were recruited,and HE and HID-AB staining(the golden standard of high-risk IM)were apllied to detect the histological types and IM types.The samples were subsequently divided into chronic inflammation group,low-risk IM group,high-risk IM group,well-differentiated intestinal-type gastric cancer group,and poorly-differentiated intestinal-type gastric cancer group.The positive rate of LCPL in each group and its diagnostic efficacy were analyzed based on endoscopic images of the biopsy sites.Logistic regression analysis was used to investigate the relationship between LCPL sign and high-risk IM,as well as the clinical and pathological features associated with LCPL sign.Receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic efficacy of LCPL for high-risk IM,using indicators such as sensitivity,specificity,Youden index and area under the curve(AUC).Results The positive rate of the LCPL sign in high-risk IM group was 75.70%,significantly higher than that of the other groups(all P<0.001).Logistic regression analysis showed that LCPL sign was significantly correlated with high-risk IM(OR=30.286,95%CI:13.528～67.804,P<0.001).When the sign was employed in diagnosing high-risk IM,the sensitivity was 69.84%,the specificity was 93.75%,the Youden's index was 0.636,and the AUC value was 0.818(95%CI:0.773～0.857).Besides sensitivity,all above parameters of LCPL sign showed significantly better diagnostic efficacy than those of traditional LBC sign,which is used as a sign for diagnosing IM(P<0.001).Moreover,recognition of LCPL sign was not easily affected by age(OR=1.130,95%CI:0.709～1.800,P=0.607),lesion site(Angular incisure:OR=2.360,95%CI:0.732～7.613,P=0.151;Autrum:OR=2.257,95%CI:0.756～6.744,P=0.145),and presence of peptic ulcers(OR=1.085,95%CI:0.208～5.652,P=0.923).Significantly,94.12%of positive and 66.94%of negative LCPL signs could be rapidly recognized within 3 s(OR=4.536,95%CI:1.372～14.997,P=0.013).Conclusion LCPL sign shows high efficacy and potential clinical application value for high-risk IM in gastric mucosa of endoscopic diagnosis.