Lymph Node Metastasis in Gastrointestinal Carcinomas: A View from a Proteomics Perspective

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors:

Proteomics technology are commonly used to identify novel biomarkers for patients with malignancy as well as prognosis prediction. The authors conducted a systemic review regarding current evidences of gastrointestinal cancer with lymph node metastasis using proteomic approaches till date. The issue is important and provide a quick review for physicians who treated patients with gastrointestinal cancers. However, there were several issues needed to be addressed in detail.

1.     The authors had a comprehensive introduction regarding the association between lymph node metastasis and angiogenesis in “2. Lymphangiogenesis and Role of Growth Factors and Chemokines”. However, most literatures cited in this section were not researches based on gastrointestinal cancer. The authors should enroll more evidences of gastrointestinal cancer in this part, rather than studies of other malignancy. 

2.     Furthermore, given that this study aimed to discuss proteomes of gastrointestinal cancer, the authors could raise some proteins which were associated with angiogenesis pathway to support their statement in this section “2. Lymphangiogenesis and Role of Growth Factors and Chemokines”.

3.     In “ 3.2. Proteomics in LN Metastatic Colorectal Carcinoma”, there were a lot of researches focusing on this topic. The authors only summarized the findings of these studies without further discussion. It will be more valuable if the authors could have a comparison between these literatures. For example, most studies used primary tumor tissue for examination except one study [42] which used lymph node as specimen source. The authors could have a comment on which tissue sources were recommended or most reliable. 

4.     Another dilemma is that each study investigated the association between one certain protein and lymph node metastasis using one certain method. The authors should have a discussion on which protein in these studies of colorectal cancer had more solid evidences as well as the advantages and disadvantages of these methods.

5.     The same situation was also found in “3.4. Proteomics in LN Metastatic Gastric Carcinoma” and “3.8. Proteomics in LN Metastatic Pancreatic Carcinoma”. The authors only summarized the findings of these studies without further discussion. The authors should have a comparison between these literatures of gastric cancer and pancreatic cancer, for example, specimen sources (primary tumor or serum?) and which protein had more solid evidences, as in colorectal cancer. 

6.     In the discussion section, the authors could have a discussion whether these proteomes were also associated with prognosis. If they were, these proteomes should be widely used in clinical practices for outcome prediction.  

Comments on the Quality of English Language

Quality of English is acceptable.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

1.        The study focuses only on six types of gastrointestinal carcinomas (GICs), leaving out other potentially relevant cancers within the gastrointestinal tract. This might limit the generalizability of the findings, given the diversity of tumors that may have specific biological characteristics. So, it's important to include mentions of all GICs.

 2.        The authors highlight the absence of high-throughput proteomics studies conducted for esophageal carcinoma and hepatocellular carcinoma. This creates gaps in understanding proteomic patterns and metastasis mechanisms for these specific cancers.

 3.        While the article provides ample data from proteomic studies, there's a lack of clinical validation of the identified biomarkers. Without confirmation in real clinical settings, it's challenging to assess the clinical utility of these biomarkers in diagnosis or therapy. The authors should explain in more detail the application of the researched data in clinical practice.

 4.        The article should have a more detailed discussion on the challenges associated with proteomic techniques and data analysis in the context of studying LNM.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear editors:

The authors have well responses to my concerns. I think this study is worth for publication.

Reviewer 2 Report

Comments and Suggestions for Authors

Authors must make the space between lines of text uniform in the article.