Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study
Abstract Background Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therap...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-11-01
|
| Series: | BMC Gastroenterology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12876-022-02521-5 |
| _version_ | 1811190485053603840 |
|---|---|
| author | Yuka Hirashita Masahide Fukuda Masaaki Kodama Yoshiyuki Tsukamoto Tadayoshi Okimoto Kazuhiro Mizukami Yoshinari Kawahara Yasuhiro Wada Sotaro Ozaka Kazumi Togo Keisuke Kinoshita Takafumi Fuchino Kensuke Fukuda Kazuhisa Okamoto Ryo Ogawa Osamu Matsunari Koichi Honda Kazunari Murakami |
| author_facet | Yuka Hirashita Masahide Fukuda Masaaki Kodama Yoshiyuki Tsukamoto Tadayoshi Okimoto Kazuhiro Mizukami Yoshinari Kawahara Yasuhiro Wada Sotaro Ozaka Kazumi Togo Keisuke Kinoshita Takafumi Fuchino Kensuke Fukuda Kazuhisa Okamoto Ryo Ogawa Osamu Matsunari Koichi Honda Kazunari Murakami |
| author_sort | Yuka Hirashita |
| collection | DOAJ |
| description | Abstract Background Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status, efficacy of eradication therapy, and GC risk in H. pylori-eradicated mucosa, and to reveal the potential downstream molecules of eEF1A dimethylation. Methods Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9 mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2. Results The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with the negative mucosa (surface, p = 0.0031; basal, p = 0.0036, respectively). The eEF1A dimethyl-levels in the surface area were significantly reduced by eradication therapy (p = 0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio = 3.6611, 95% confidence interval = 1.0350–12.949, p = 0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors, Oct4 and Nanog, by immunohistochemistry and in vitro genome editing experiments. Conclusions The results indicated that H. pylori infection induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori eradicated-gastric mucosa. |
| first_indexed | 2024-04-11T14:51:57Z |
| format | Article |
| id | doaj.art-9e80dd81703340f085ffef531f7c2128 |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-04-11T14:51:57Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-9e80dd81703340f085ffef531f7c21282022-12-22T04:17:26ZengBMCBMC Gastroenterology1471-230X2022-11-0122111010.1186/s12876-022-02521-5Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational studyYuka Hirashita0Masahide Fukuda1Masaaki Kodama2Yoshiyuki Tsukamoto3Tadayoshi Okimoto4Kazuhiro Mizukami5Yoshinari Kawahara6Yasuhiro Wada7Sotaro Ozaka8Kazumi Togo9Keisuke Kinoshita10Takafumi Fuchino11Kensuke Fukuda12Kazuhisa Okamoto13Ryo Ogawa14Osamu Matsunari15Koichi Honda16Kazunari Murakami17Department of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Molecular Pathology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityDepartment of Gastroenterology, Faculty of Medicine, Oita UniversityAbstract Background Although eradication therapy for chronic Helicobacter pylori (H. pylori) reduces the risk of gastric cancer (GC), its effectiveness is not complete. Therefore, it is also critically important to identifying those patients who remain at high risk after H. pylori eradication therapy. Accumulation of protein methylation is strongly implicated in cancer, and recent study showed that dimethylation of eEF1A lysine 55 (eEF1AK55me2) promotes carcinogenesis in vivo. We aimed to investigate the relationship between eEF1A dimethylation and H. pylori status, efficacy of eradication therapy, and GC risk in H. pylori-eradicated mucosa, and to reveal the potential downstream molecules of eEF1A dimethylation. Methods Records of 115 patients (11 H. pylori-negative, 29 H. pylori-positive, 75 post-eradication patients) who underwent upper gastrointestinal endoscopy were retrospectively reviewed. The eEF1A dimethyl level was evaluated in each functional cell type of gastric mucosa by immunofluorescent staining. We also investigated the relationship between eEF1AK55me2 downregulation by CRISPR/Cas9 mediated deletion of Mettl13, which is known as a dimethyltransferase of eEF1AK55me2. Results The level of eEF1A dimethylation significantly increased in the surface and basal areas of H. pylori-positive mucosa compared with the negative mucosa (surface, p = 0.0031; basal, p = 0.0036, respectively). The eEF1A dimethyl-levels in the surface area were significantly reduced by eradication therapy (p = 0.005), but those in the basal area were maintained even after eradication therapy. Multivariate analysis revealed that high dimethylation of eEF1A in the basal area of the mucosa was the independent factor related to GC incidence (odds ratio = 3.6611, 95% confidence interval = 1.0350–12.949, p = 0.0441). We also showed the relationship between eEF1A dimethylation and expressions of reprogramming factors, Oct4 and Nanog, by immunohistochemistry and in vitro genome editing experiments. Conclusions The results indicated that H. pylori infection induced eEF1A dimethylation in gastric mucosa. The accumulation of dimethyl-eEF1A in the basal area of the mucosa might contribute to GC risk via regulation of reprograming factors in H. pylori eradicated-gastric mucosa.https://doi.org/10.1186/s12876-022-02521-5Atrophic gastritisGastric cancerMethylationRisk factor |
| spellingShingle | Yuka Hirashita Masahide Fukuda Masaaki Kodama Yoshiyuki Tsukamoto Tadayoshi Okimoto Kazuhiro Mizukami Yoshinari Kawahara Yasuhiro Wada Sotaro Ozaka Kazumi Togo Keisuke Kinoshita Takafumi Fuchino Kensuke Fukuda Kazuhisa Okamoto Ryo Ogawa Osamu Matsunari Koichi Honda Kazunari Murakami Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study BMC Gastroenterology Atrophic gastritis Gastric cancer Methylation Risk factor |
| title | Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study |
| title_full | Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study |
| title_fullStr | Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study |
| title_full_unstemmed | Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study |
| title_short | Potential association of eEF1A dimethylation at lysine 55 in the basal area of Helicobacter pylori-eradicated gastric mucosa with the risk of gastric cancer: a retrospective observational study |
| title_sort | potential association of eef1a dimethylation at lysine 55 in the basal area of helicobacter pylori eradicated gastric mucosa with the risk of gastric cancer a retrospective observational study |
| topic | Atrophic gastritis Gastric cancer Methylation Risk factor |
| url | https://doi.org/10.1186/s12876-022-02521-5 |
| work_keys_str_mv | AT yukahirashita potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT masahidefukuda potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT masaakikodama potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT yoshiyukitsukamoto potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT tadayoshiokimoto potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT kazuhiromizukami potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT yoshinarikawahara potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT yasuhirowada potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT sotaroozaka potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT kazumitogo potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT keisukekinoshita potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT takafumifuchino potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT kensukefukuda potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT kazuhisaokamoto potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT ryoogawa potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT osamumatsunari potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT koichihonda potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy AT kazunarimurakami potentialassociationofeef1adimethylationatlysine55inthebasalareaofhelicobacterpylorieradicatedgastricmucosawiththeriskofgastriccanceraretrospectiveobservationalstudy |