One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy

Round 1

Reviewer 1 Report (Previous Reviewer 3)

I think the authors solved all my concerns in this version. I don't have any comments to add this time. I think this version should be published. 

Reviewer 2 Report (Previous Reviewer 2)

Dear Editor, 

The authors have addressed, adequately, all my concerns, and I am confident to suggest the article for publication in the journal.

 

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Well written paper. No recommendation needs to be given.

Reviewer 2 Report

ijms-1971333

“One third of MPM shows high immunohistochemical expression (Score 3+) of MSLN or CXCR4 – possible candidates for endo-radiotherapy?”

Hager et al.

 

Dear Editor,

In the following manuscript “One third of MPM shows high immunohistochemical expression (Score 3+) of MSLN or CXCR4 – possible candidates for endo-radiotherapy?”, by Hager et al., submitted for publication in the International Journal of Molecular Sciences, authors have summarized the data accumulated through the screening of Mesothelin (MSLN) and CXCR4 expression levels in tumor specimens from 105 patients suffering from Malignant pleural mesothelioma (MPM). The samples were collected during the patient treatment at the Lung Cancer Centre of Essen (between 2006 and 2009) and at the Helios Klinikum Emil von Behring Berlin (between 2002 and 2009). Authors have performed immunohistochemical staining to investigate by semiquantitative method the expression patters of MSLN and CXCR4 (two well-known proteins, which are selectively expressed in tumor tissues and which could be targeted by immunotherapy and radiopharmaceutical ligands). The reported results demonstrate a strong correlation between the increased expression level of CXCR4 and at lower degree the MSLN and the development of MPM.

Although the current study is highly specialized and cover topics, which may not be completely understandable by the broad audience, it possesses a great potential to establish fundamental basis for efficient MPM treatment strategies. The investigation of the MSLN and CXCR4 expression patterns in MPM patients, could provide a valuable information, which latter could be harness to increase the efficacy of MPM treatment strategies and to facilitate the development of new more effective regimens for MPM.

However, despite the great potential, the article requires some improvements in order to deliver its message properly. Please, find below my detailed comments and suggestions:

1.      My major concern is that the article is very specialized and may not generate a desired impact in its current form. However, the study reports a valuable observation, which required recognition. Therefore, it is highly recommended authors to improve the presentation and to clearly define the background and the purpose of the current study.

2.      Another obvious negative feature of the study is the choice of analysis. As authors have mentioned they have applied semiquantitative method to analyze the expression levels of MSLN and CXCR4. This approach is very subjective and rely on the judgement of the investigator, which decrease significantly the quality of the obtained data. I will strongly recommend more unbiased approach to be implemented in the analysis. There are multiple free software packages, which provide a strong background for quantitative analyses of histological data.

3.      The style and the presentation of the article could be improved by clear explanation of the general idea and simplification of the overall expressions. This is true particularly for the abstract, which should be edited to reflect better the overall message of the study.

4.      A high magnification set of immunohistochemistry stained images will further increase the presentation quality of the data. This is especially helpful for the current study, where membrane and nuclear proteins are investigated.

5.      A table with a detailed statistical analysis data, provided as a supplementary information, will be also highly beneficial.

6.      There are increased number of abbreviations, which are not indicated at their first appearance. It is recommended all the abbreviations to be indicated at their first appearance. This will facilitate the smooth reading of the article.

7.      Authors may decide to improve the title as the abbreviation (MPM) and the Score3+, do not contribute very well for its better understanding. Moreover, the question mark is not fully appropriate.

Reviewer 3 Report

Overall, this is a very well-written manuscript. The authors gave a very detailed background/introduction and clear design. The result part was easy to follow and understand. The forest plot was very straightforward. The discussion was also fully depicted. 

 

Major concerns:

1. wondering if the authors could put the methods part right after the introduction part, this will make the readers easy to understand the following analysis;

2. for the method part, the author mentioned ANOVA analysis, I think group-wise comparison test should also be added like Tukey's HSD test, once the ANOVA test is significant (should be used for figure 3?);

3. For the survival analysis, is that univariate cox model? or multivariate cox model? Could the authors provide more details about what covariates were adjusted for if there was any?

4. I strongly suggest the authors run a baseline univariate/descriptive analysis, since the difference between baseline covariates may contribute to the significance of the outcome model.