Effect of Baseline Characteristics and Tumor Burden on Vaspin Expression and Progressive Disease in Operable Colorectal Cancer

Round 1

Reviewer 1 Report

The study by Kan et al. aimed to investigate the influence of baseline characteristics and tumor burden on tumor marker expression and progressive colorectal cancer. The authors analyzed 89 tissue samples of CRC patients using immunohistochemistry and used a PLS-PM approach to evaluate the relationship between prognostic variables and progressive disease status. Performing IHC analyses on colorectal biopsies of CRC patients, the authors reported a generally higher vaspin expression in progressive disease patients. Therefore, the authors claim vaspin to be a potential indicator of colorectal cancer progression with expression potentially influenced by baseline characteristics such as age, sex and BMI. The PLS-PM approach has not been applied before to investigate vaspin expression in the context of tumor burden and cancer progression.

Using a PLS-PM approach allows estimation of cause-effect relationships also with small sample sizes and the authors discuss limitations arising from the retrospective approach and the limited sample size. And while this reviewer cannot evaluate the validity of the authors partial least squares path-modeling approach used to evaluate cause-effect relationship models, the evidence and quantification of vaspin expression based on the presented histological data are not very convincing.

Major concerns:

Analyzing CRC samples in dependency of tumor stage, tumor size and lymph node invasion, the authors could only find a significant difference in vaspin expression in the T3-4 subgroup. However, especially these histological images are not very convincing. Moreover, some stainings (e.g. N0 subgroup) seem to be unspecific.  Did the authors test other antibodies? Please include all relevant histological controls to demonstrate specificity of the stainings.

The authors also need to specify on the cell type of these apparently vaspin expressing cells (endocrine cells, enterocytes, goblet cells etc.)?

Histological scores were determined as percentage of cytoplasmic staining solely in tumor cells. As vaspin expression seems to be influenced by patients baseline characteristics (e.g.  body weight, DM status), as is known and widely published for vaspin serum levels, the question arises of how vaspin is expressed in non-tumorigenic cells in comparison to tumorigenic cells in patients with progressive disease?

Minor points:

Why did the authors did only include male patients in their study?

Based on two prospective studies (12,13 ) the authors hypothesize that vaspin fulfills a specific function and role in cancer. Both of these studies are entirely descriptive and do not provide any mechanistic insights and results furthermore contradict each other.  

In general, the cited literature on vaspin is neglecting the major publications and specific to those focusing on distinct subpopulations. The authors should expand and include literature with regard to the established vaspin actions in inflammation and (metabolic) disease.

The cited study (18) on vaspin and colorectal cancer examined the relationship of vaspin serum levels and CRC. Did the authors check circulating levels in their patients?

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 2 Report

Dear Authors,

You prepared manuscript on very rare topic, what is a good point in my opinion.

I have a few comments:

1. You wrote that colorectal cancer is highly heterogenous maligancy in the Asian population, what about European population or Americas population?
2. You used some acronyms before you wrote firstly full words.
3. In part 2.2 statistical analysis is reference no. 34, the  last previous references is no. 19? Why?? 
4. Why do you present these results so late?... You had collected them between 2006 and 2007

Author Response

Please see the attachment.

Author Response File: Author Response.docx

Reviewer 3 Report

Thank you for request of my opinion. 
The paper is interesting, the theme is original.
I think that the results are weak, and for this reason I don't think that the tumor burden on vaspin expression can give a good contribute to prediction or evidence for colorectal cancer progression.
In any case, I think that the theme is new and original, and it can give a contribute of knowledge for the scientific literature. 

Author Response

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The authors have tried to adress the major points.

Reviewer 2 Report

Dear Authors,

I am satisfied with your reply.

Good job!