Title: CLDN18.2 Expression and Its Impact on Prognosis and the Immune Microenvironment
in Gastric Cancer
Version: 1 Date: 13 Jul 2023
Reviewer's report:
Thank you for gave me the opportunity to revise this interesting paper about CLDN18.2
Expression and its Impact on Prognosis and Immune Microenvironment in Gastric Cancer.
I found the topic of interest and the paper well written.
However, I suggest making some changes in order to improve the quality of the manuscript.
In particular, I suggest:
Major:
- to clarify what do you mean for paracancerous tissue. In particular, in the discussion the authors
state that "In our cohort of 342 gastric tumor tissues and their corresponding adjacent tissues...".
However, when they cited paracancerous tissue in the material and method section, it is not clear
what is a paracancerous tissue (normal tissue?) and if those tissues were from the same patient
in pairs (tumour/normal tissue). Please add some comments on that and revise those sections
accordingly;
- to clarify the cut off used to define PDL1 positive and PDL1 negative. In fact, even though
the authors have described the type of analysis (“The expression of PD-L1 was evaluated using
the combined positive score (CPS), etc”), they concluded that “based on the median number of
stained cells, patients were categorized into high and low expression groups.”. However, the cut
off is not clear and this might affect the results. Please, clarify this issue, add the cut-off and
modify all accordingly.
- to add clearly all the limitations of the analysis. Among them, I suggest to add a comment
regarding the value of PDL1 ant tumour microenvironment cells evaluated on samples collected
from March 2008 to August 2017 (ancient archival blocks).
Minor:
- in the introduction, please specify the phase of the trials you have cited, eg  FAST and MONO
trials are phase 2 trials;
- in the introduction, please add the recently presented preliminary results of SPOTLIGHT trial;
- to carefully revise the paper to avoid typos (e.g Lauran- in the text, in the figures, etc)
- to revise the abbreviation in order to use them at the first appearance (eg. IHC, GC and so on);
- to revise the references regarding GLOBOCAN in order to be sure to use the same newest
version (see references 1 and 28);
- The authors found that “CLDN18.2 expression levels are associated with the degree of
tumor differentiation, Borrmann type, and PD-L1 expression levels.”.  However, in the first
sentence they state “the expression level of CLDN18.2 in gastric cancer showed little significant
correlation with various clinicopathological characteristics, except for the level of PD-L1
expression (p = 0.004).” It is a bit confounding. Please clarify the issue about PDL1.
- Please show data about the multivariate Cox analysis in a table.
Title: CLDN18.2 Expression and Its Impact on Prognosis and the Immune Microenvironment
in Gastric Cancer
Version: 1 Date: 13 Jul 2023
Reviewer's report:
Thank you for gave me the opportunity to revise this interesting paper about CLDN18.2
Expression and its Impact on Prognosis and Immune Microenvironment in Gastric Cancer.
I found the topic of interest and the paper well written.
However, I suggest making some changes in order to improve the quality of the manuscript.
In particular, I suggest:
Major:
- to clarify what do you mean for paracancerous tissue. In particular, in the discussion the authors
state that "In our cohort of 342 gastric tumor tissues and their corresponding adjacent tissues...".
However, when they cited paracancerous tissue in the material and method section, it is not clear
what is a paracancerous tissue (normal tissue?) and if those tissues were from the same patient
in pairs (tumour/normal tissue). Please add some comments on that and revise those sections
accordingly;
- to clarify the cut off used to define PDL1 positive and PDL1 negative. In fact, even though
the authors have described the type of analysis (“The expression of PD-L1 was evaluated using
the combined positive score (CPS), etc”), they concluded that “based on the median number of
stained cells, patients were categorized into high and low expression groups.”. However, the cut
off is not clear and this might affect the results. Please, clarify this issue, add the cut-off and
modify all accordingly.
- to add clearly all the limitations of the analysis. Among them, I suggest to add a comment
regarding the value of PDL1 ant tumour microenvironment cells evaluated on samples collected
from March 2008 to August 2017 (ancient archival blocks).
Minor:
- in the introduction, please specify the phase of the trials you have cited, eg  FAST and MONO
trials are phase 2 trials;
- in the introduction, please add the recently presented preliminary results of SPOTLIGHT trial;
- to carefully revise the paper to avoid typos (e.g Lauran- in the text, in the figures, etc)
- to revise the abbreviation in order to use them at the first appearance (eg. IHC, GC and so on);
- to revise the references regarding GLOBOCAN in order to be sure to use the same newest
version (see references 1 and 28);
- The authors found that “CLDN18.2 expression levels are associated with the degree of
tumor differentiation, Borrmann type, and PD-L1 expression levels.”.  However, in the first
sentence they state “the expression level of CLDN18.2 in gastric cancer showed little significant
correlation with various clinicopathological characteristics, except for the level of PD-L1
expression (p = 0.004).” It is a bit confounding. Please clarify the issue about PDL1.
- Please show data about the multivariate Cox analysis in a table.
Please review this paper.
user
Title: CLDN18.2 Expression and Its Impact on Prognosis and the Immune Microenvironment
in Gastric Cancer
Version: 1 Date: 13 Jul 2023
Reviewer's report:
Thank you for gave me the opportunity to revise this interesting paper about CLDN18.2
Expression and its Impact on Prognosis and Immune Microenvironment in Gastric Cancer.
I found the topic of interest and the paper well written.
However, I suggest making some changes in order to improve the quality of the manuscript.
In particular, I suggest:
Major:
- to clarify what do you mean for paracancerous tissue. In particular, in the discussion the authors
state that "In our cohort of 342 gastric tumor tissues and their corresponding adjacent tissues...".
However, when they cited paracancerous tissue in the material and method section, it is not clear
what is a paracancerous tissue (normal tissue?) and if those tissues were from the same patient
in pairs (tumour/normal tissue). Please add some comments on that and revise those sections
accordingly;
- to clarify the cut off used to define PDL1 positive and PDL1 negative. In fact, even though
the authors have described the type of analysis (“The expression of PD-L1 was evaluated using
the combined positive score (CPS), etc”), they concluded that “based on the median number of
stained cells, patients were categorized into high and low expression groups.”. However, the cut
off is not clear and this might affect the results. Please, clarify this issue, add the cut-off and
modify all accordingly.
- to add clearly all the limitations of the analysis. Among them, I suggest to add a comment
regarding the value of PDL1 ant tumour microenvironment cells evaluated on samples collected
from March 2008 to August 2017 (ancient archival blocks).
Minor:
- in the introduction, please specify the phase of the trials you have cited, eg  FAST and MONO
trials are phase 2 trials;
- in the introduction, please add the recently presented preliminary results of SPOTLIGHT trial;
- to carefully revise the paper to avoid typos (e.g Lauran- in the text, in the figures, etc)
- to revise the abbreviation in order to use them at the first appearance (eg. IHC, GC and so on);
- to revise the references regarding GLOBOCAN in order to be sure to use the same newest
version (see references 1 and 28);
- The authors found that “CLDN18.2 expression levels are associated with the degree of
tumor differentiation, Borrmann type, and PD-L1 expression levels.”.  However, in the first
sentence they state “the expression level of CLDN18.2 in gastric cancer showed little significant
correlation with various clinicopathological characteristics, except for the level of PD-L1
expression (p = 0.004).” It is a bit confounding. Please clarify the issue about PDL1.
- Please show data about the multivariate Cox analysis in a table.
assistant