Prognostic Significance of CXCR4 in Colorectal Cancer: An Updated Meta-Analysis and Critical Appraisal

Round 1

Reviewer 1 Report

Revievers comments were adressed. A limitations section was included.  If the editors feel, that the originality of the paper meets the standard of the journal, then this is a well-written manuscript; well structured, comfortable to read and the methodology is sound. I have no further comments.

I want to congratulate the authors on their manuscript and their hard work

Author Response

Thanks for such consideration to our manuscript and the constructive revision.

Reviewer 2 Report

No more comments

Author Response

Thanks for the time and the attention spent for our manuscript.

Reviewer 3 Report

Alessandro Ottaiano et al. performed a systemic review and meta-analysis to evaluate the association between CXCR4 and colorectal cancer.

This study encompasses an interesting topic.

1. Although all studies were retrospective study, this meta-analysis implies important finding. However, future prospective study should be needed. Authors should discuss what future study are able to clarify the role of CXCR4 on the prognosis of colorectal cancer.
2. Authors documented their plan to perform prospective study. Please consider to discuss the design of the study and estimated sample size according to this meta-analysis.
3. Section 3 is result. Section 5 is conclusion. I cannot find section 4.
4. Authors discuss something in the conclusion section. Please separate them into discussion section and conclusion section.

Author Response

Reviewer#3

This study encompasses an interesting topic.

Point#1

Although all studies were retrospective study, this meta-analysis implies important finding. However, future prospective study should be needed. Authors should discuss what future study are able to clarify the role of CXCR4 on the prognosis of colorectal cancer.

Authors: 

Thank you for prompting us to propose “what future study…”. As declared by the Reviewer Her/Himself and as we already stated in Discussion, the only way to confirm or not the prognostic role of CXCR4 is to conduct a prospective study. Please, see the response at point 2 as they are interconnected.

Point#2

Authors documented their plan to perform prospective study. Please consider to discuss the design of the study and estimated sample size according to this meta-analysis.

Authors: 

Following your suggestion we have added this section to the revised version of the manuscript: “Assessment of CXCR4 will be performed through IHC according to a previously published homogeneous evaluation method (negative, low, high) (24, 25). The hypothesis of the study is based on the following statistical assumptions: i) HR for high expression of CXCR4 of 2.09 (vs negative/low), ii) test power of 80%, iii) alpha value of the I-type error of 5%, and iv) median survival of 18 months (in unselected mCRC patients). The survival curves will be depicted with the Kaplan-Meier method and the statistical significance verified with a two-tailed log-rank test. The final sample is 200 patients.”

Point#3

Section 3 is result. Section 5 is conclusion. I cannot find section 4.

Authors: 

Sorry for the mistake. As noticed by the Reviewer#3 we have wrongly fused Discussion and Conclusions. Please, see also point 4 in the revised version of the manuscript.

Point#4

Authors discuss something in the conclusion section. Please separate them into discussion section and conclusion section.

Authors: 

As correctly suggested by the Referee, we have done this in the revised version of the manuscript.

Round 2

Reviewer 3 Report

I think that this manuscript has a benefit to publish and authors answered all comments, which I provided, and revised the manuscript well.