Liquid Biopsy for Colorectal Cancer: Advancing Detection and Clinical Application
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript by Lee et al. summarizes some of the methods used to detect CRC.
The authors describe the use of liquid biopsy as a non-invasive approach to detect colorectal cancer based on circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and RNA-based biomarkers such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), as well as tumor-derived platelets (TEPs).
In abstract authors write: ‘These methods provide valuable insights into genetic and epigenetic tumor alterations’
What methods do they mean?
It is difficult to understand the semantic transition after listing the types of liquid biopsy mentioned above.
- The authors overlooked one of the most important biomarkers - methylation-based biomarkers that can be used to diagnose colorectal cancer and confirm the presence of ctDNA.
- Methylation-specific biomarkers play a crucial role in early detection, prognosis, and treatment monitoring of colorectal cancer (CRC). In CRC, abnormal methylation patterns contribute to tumor initiation and progression, making them valuable biomarkers for non-invasive detection.
- Methylation-specific biomarkers offer a powerful tool for CRC screening, prognosis, and therapy selection. FDA-approved tests like Epi proColon® and Cologuard® already utilize these markers for early detection.
The manuscript must be edited in English to have a scientific sound.
Author Response
Comment 1:
The manuscript by Lee et al. summarizes some of the methods used to detect CRC. The authors describe the use of liquid biopsy as a non-invasive approach to detect colorectal cancer based on circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and RNA-based biomarkers such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), as well as tumor-derived platelets (TEPs). In abstract authors write: ‘These methods provide valuable insights into genetic and epigenetic tumor alterations’ What methods do they mean? It is difficult to understand the semantic transition after listing the types of liquid biopsy mentioned above.
Response: We sincerely thank the reviewer for this insightful comment. The methods referred to in the abstract include the various liquid biopsy approaches mentioned in the manuscript, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), long non-coding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), and tumor-educated platelets (TEPs).
Comment 2:
The authors overlooked one of the most important biomarkers - methylation-based biomarkers that can be used to diagnose colorectal cancer and confirm the presence of ctDNA. Methylation-specific biomarkers play a crucial role in early detection, prognosis, and treatment monitoring of colorectal cancer (CRC). In CRC, abnormal methylation patterns contribute to tumor initiation and progression, making them valuable biomarkers for non-invasive detection. Methylation-specific biomarkers offer a powerful tool for CRC screening, prognosis, and therapy selection. FDA-approved tests like Epi proColon® and Cologuard® already utilize these markers for early detection.
Response: We sincerely thank the reviewer for this insightful comment. We would also like to clarify that methylation-based biomarkers, particularly hypermethylated DNA such as methylated SEPT9, are discussed as part of the ctDNA section (page 6, paragraph 2). To address the reviewer’s valuable suggestion, we have further expanded this section to provide more detailed discussion on methylation-based biomarkers and included additional references to highlight their significance and clinical utility in CRC detection. We appreciate the reviewer’s thoughtful feedback, which has helped us improve the clarity and comprehensiveness of our manuscript.
Comment 3:
The manuscript must be edited in English to have a scientific sound.
Response: We sincerely thank the reviewer for this insightful comment, the revised manuscript has been professionally reviewed and edited by a native English speaker specialized in biomedical sciences to ensure clarity and correctness.
Reviewer 2 Report
Comments and Suggestions for AuthorsDear Authors
Review article explains and concludes well that - The current key liquid biopsy modalities in CRC include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and RNA-based biomarkers such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), and tumor educated platelets (TEPs).
Minor corrections are required
The following steps should provide more clear information for readers to enjoy it
1) Please add up-to-date references in the introduction and discussion section.
2) Please keep a graphical abstract.
Author Response
Review article explains and concludes well that - The current key liquid biopsy modalities in CRC include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and RNA-based biomarkers such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), and tumor educated platelets (TEPs).
Minor corrections are required
The following steps should provide more clear information for readers to enjoy it
1) Please add up-to-date references in the introduction and discussion section.
2) Please keep a graphical abstract.
Comment 1
Please add up to date references in the introduction and discussion section.
Response:
We sincerely thank the reviewer for this insightful comment. In response, we have carefully reviewed and updated the references in both the introduction and discussion sections, incorporating the most recent and relevant studies to ensure the content reflects current advancements in the field.
Comment 2
Please keep a graphical abstract.
Response:
Thank you for your thoughtful suggestion. If the reviewer is referring to a summary figure, we would like to clarify that we have included a comprehensive summary table of potential lncRNAs involved in CRC, which we believe effectively presents and organizes the key information for readers. At this time, we feel that this table serves the purpose of summarizing the content without the need for an additional graphical figure.
However, if a graphical abstract is required for publication purposes, we are happy to prepare and submit one upon request.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors generally responded to the reviewers' comments.
The revised manuscript was improved and included an important paragraph regarding the use of DNA methylation markers and their detection in ctDNA.
