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
Version: 1 Date: 21 May 2022
Reviewer's report:
The authors investigated the relationship between eEF1A dimethylation and H. pylori status in
gastric mucosa and to reveal potential downstream molecules of eEF1A dimethylation in H.
pylori-eradicated mucosa. And the authors found that 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.
This manuscript was well covered the diagnostic tools for GC diagnosis currently available.
Especially in endoscopy section, the authors described about the endoscopic diagnostic
technique from white light to LCI in detail. In contrast, in Barium meal section, the description
volume is small. If the authors find good reference for this method, please describe a little bit
more.
Anyway, to detect GC in early stage with non-invasive method is most important thing. As the
authors mentioned in conclusion section, new diagnostic markers (e.g. exosomes) are the hope
for the non-invasive diagnostic tools.
Please clarify these points described below.
About evaluation of dimethyl eEF1A level, it seems the authors picked up only three areas from
each histological sample. When I see one sample as you showed, the intensities were varied in
the sample. So if the authors picked up three areas from dark area, the result will be low. Taking
many picking area are better for this kind of study.
The sentences from lone 180 in p10 “Because there were age differences between these three
groups (Table 1), we also calculated the age-adjusted levels of eEF1A dimethylation and
compared them between the groups using analysis of covariance with the Tukey test. We
found the same tendency in both the crude and age-adjusted models, indicating that age-related
differences in methylation did not account for the results (Figure 1b). These results suggested
that the dimethylation of eEF1A in the basal level remained high in atrophic gastric mucosa even
after H. pylori eradication therapy” should be describe dand discussed in discussion section.
The sentences from line 212 in page 12 “In recent reports, chief cells have been identified as
a cell capable of reprogramming and metaplastic response to parietal cell damage in atrophic
gastric mucosa [23, 24]. Octamer-binding transcription factor 4 (OCT4), and Nanog lie in the
core of the transcriptional network that controls stem cell pluripotency [25].” Should be written
in introduction or discussionsection.
What is TMK-1 cell line. Please explain about this cell line.
It is not clear that the relations among dimethyl eEF1A, Oct4 and Nanog. Please describe these
associations about these molecukes especially Oct4 and Nanog. What is the difference between
Oct4 and Nanog?
Minor points:
Usually, the statistical analysis section is the last in Methods.
The authors performed knockout of Mettl13, however the explanation about this molecule was
described in results section. I think the explanation should be in introduction or methods. How
do you think?
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
Version: 1 Date: 21 May 2022
Reviewer's report:
The authors investigated the relationship between eEF1A dimethylation and H. pylori status in
gastric mucosa and to reveal potential downstream molecules of eEF1A dimethylation in H.
pylori-eradicated mucosa. And the authors found that 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.
This manuscript was well covered the diagnostic tools for GC diagnosis currently available.
Especially in endoscopy section, the authors described about the endoscopic diagnostic
technique from white light to LCI in detail. In contrast, in Barium meal section, the description
volume is small. If the authors find good reference for this method, please describe a little bit
more.
Anyway, to detect GC in early stage with non-invasive method is most important thing. As the
authors mentioned in conclusion section, new diagnostic markers (e.g. exosomes) are the hope
for the non-invasive diagnostic tools.
Please clarify these points described below.
About evaluation of dimethyl eEF1A level, it seems the authors picked up only three areas from
each histological sample. When I see one sample as you showed, the intensities were varied in
the sample. So if the authors picked up three areas from dark area, the result will be low. Taking
many picking area are better for this kind of study.
The sentences from lone 180 in p10 “Because there were age differences between these three
groups (Table 1), we also calculated the age-adjusted levels of eEF1A dimethylation and
compared them between the groups using analysis of covariance with the Tukey test. We
found the same tendency in both the crude and age-adjusted models, indicating that age-related
differences in methylation did not account for the results (Figure 1b). These results suggested
that the dimethylation of eEF1A in the basal level remained high in atrophic gastric mucosa even
after H. pylori eradication therapy” should be describe dand discussed in discussion section.
The sentences from line 212 in page 12 “In recent reports, chief cells have been identified as
a cell capable of reprogramming and metaplastic response to parietal cell damage in atrophic
gastric mucosa [23, 24]. Octamer-binding transcription factor 4 (OCT4), and Nanog lie in the
core of the transcriptional network that controls stem cell pluripotency [25].” Should be written
in introduction or discussionsection.
What is TMK-1 cell line. Please explain about this cell line.
It is not clear that the relations among dimethyl eEF1A, Oct4 and Nanog. Please describe these
associations about these molecukes especially Oct4 and Nanog. What is the difference between
Oct4 and Nanog?
Minor points:
Usually, the statistical analysis section is the last in Methods.
The authors performed knockout of Mettl13, however the explanation about this molecule was
described in results section. I think the explanation should be in introduction or methods. How
do you think?
Please review this paper.
user
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
Version: 1 Date: 21 May 2022
Reviewer's report:
The authors investigated the relationship between eEF1A dimethylation and H. pylori status in
gastric mucosa and to reveal potential downstream molecules of eEF1A dimethylation in H.
pylori-eradicated mucosa. And the authors found that 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.
This manuscript was well covered the diagnostic tools for GC diagnosis currently available.
Especially in endoscopy section, the authors described about the endoscopic diagnostic
technique from white light to LCI in detail. In contrast, in Barium meal section, the description
volume is small. If the authors find good reference for this method, please describe a little bit
more.
Anyway, to detect GC in early stage with non-invasive method is most important thing. As the
authors mentioned in conclusion section, new diagnostic markers (e.g. exosomes) are the hope
for the non-invasive diagnostic tools.
Please clarify these points described below.
About evaluation of dimethyl eEF1A level, it seems the authors picked up only three areas from
each histological sample. When I see one sample as you showed, the intensities were varied in
the sample. So if the authors picked up three areas from dark area, the result will be low. Taking
many picking area are better for this kind of study.
The sentences from lone 180 in p10 “Because there were age differences between these three
groups (Table 1), we also calculated the age-adjusted levels of eEF1A dimethylation and
compared them between the groups using analysis of covariance with the Tukey test. We
found the same tendency in both the crude and age-adjusted models, indicating that age-related
differences in methylation did not account for the results (Figure 1b). These results suggested
that the dimethylation of eEF1A in the basal level remained high in atrophic gastric mucosa even
after H. pylori eradication therapy” should be describe dand discussed in discussion section.
The sentences from line 212 in page 12 “In recent reports, chief cells have been identified as
a cell capable of reprogramming and metaplastic response to parietal cell damage in atrophic
gastric mucosa [23, 24]. Octamer-binding transcription factor 4 (OCT4), and Nanog lie in the
core of the transcriptional network that controls stem cell pluripotency [25].” Should be written
in introduction or discussionsection.
What is TMK-1 cell line. Please explain about this cell line.
It is not clear that the relations among dimethyl eEF1A, Oct4 and Nanog. Please describe these
associations about these molecukes especially Oct4 and Nanog. What is the difference between
Oct4 and Nanog?
Minor points:
Usually, the statistical analysis section is the last in Methods.
The authors performed knockout of Mettl13, however the explanation about this molecule was
described in results section. I think the explanation should be in introduction or methods. How
do you think?
assistant