PONE-D-21-36174Analysis of the expression of cathepsin S in gastric adenocarcinoma and in Helicobacter pylori infectionPLOS ONE

Dear Dr. Adriano Carneiro Costa,

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This is important study, but has several concerns as mentioned by the reviewer. I hope you can revise the manuscript based on the comments.

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: In this study, Costa et al. have evaluated the expression of cathepsin S in gastric cancer and H. pylori infection. The study has reported excellent findings; however, before publication, several points deserve the authors’ attention.

Major comments

Abstract

1. Results. In the gastritis group, CTTS expression was significantly higher in patients with positive test for H. pylori than negative test for H. pylori: 87.5% and 38.5%, respectively (p<0.001).

Introduction

1. Paragraph 1. Move…… (cathepsin B, H, K, L, and S) after…….at least five (………) have ……..

2. Paragraph 2. Epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and tumor growth factor-beta (TGFβ),………….

3. Paragraph 2. Activated cathepsins hydrolyze growth factors, EGF, VEGF, and TGFβ, promoting cancer cell proliferation and angiogenesis,……….. The sentence is a bit confusing, after hydrolysis if they are destroyed then how cell proliferation occurs. The hydrolysis renders maturation of the EGF, VEGF, and TGFβ, then promotes the cancer cell proliferation.

Materials and Methods

1. Study design. Paragraph 1, line 7. ….. and other with a negative result for H. pylori (n=25).

2. For the sake of understanding it is better to name the tables in immunohistochemistry as Table 1, 2, and 3 and their title or it can be also expressed in text forms. The second table is the grading of CTTS stained cells of cancer and gastritis both or only tumor cells, not clear. In the demographic data table there are CTTS stained cells in both cancer and gastritis groups but in methods, you mentioned the grading of tumor cells.

Results

1. Table 1 title. Comparison between gastric cancer and gastritis groups (demographic data)

2. Table 1, Percentage of CTTS stained cells. In the methods, the percentage has been evaluated for cancer cells only but here in gastritis also. It needs clarification

3. Paragraph 3. The explanation in the paragraph does not match Table 3. Table 3 does not contain characteristics of gastric adenocarcinoma.

4. Paragraph 4. The explanation in paragraph and figure 1 legend does not corroborate. In the paragraph, it is mentioned gastritis whereas figure 1 legend depicts gastric adenocarcinoma.

5. Paragraph 5. Similar to the above comment, the explanation in paragraph 5 and figure 2 legend does not corroborate. In the paragraph, it is explained about gastric cancer and figure 2 legend it is about gastritis.

Discussions

1. Cathepsins that have previously………….. are B, E, K, L, S, X, and Z. Provide references

2. Paragraph 2, Last sentence. The results of these studies suggest………… Which studies you are referring is not clear.

3. Provide full form when you are referring first time and then short form; for example, provide full form of TNM

Minor comments

1. Three terms; gastric tumour, gastric cancer, and gastric adenocarcinoma have been used. I suggest using either one and making it uniform.

2. Throughout the manuscript, H. pylori should be italic

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Reviewer #1: No

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Analysis of cathepsin S expression in gastric adenocarcinoma and in Helicobacter pylori infection

PONE-D-21-36174R1

Dear Dr. Adriano Carneiro Costa,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Yoshio Yamaoka

Academic Editor

PLOS ONE

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