Pancreatic Tumorigenesis: Precursors, Genetic Risk Factors and Screening

Round 1

Reviewer 1 Report (Previous Reviewer 3)

I maintain my previous opinion. The paper is well written and is a very good summary many novel things that regarding pancreatic cancer that were recently published. 

Author Response

Pancreatic Tumorigenesis: Precursors, Genetic Risk Factors and Screening, [Current Oncology] Manuscript ID: curroncol-2004173

We would like to thank the learned reviewers and editor for consideration of our manuscript for publication and thoroughly appreciate the time taken to provide us with valuable comments to improve the readability and value of our contribution to literature.

Thanks

the team  

Reviewer 2 Report (New Reviewer)

In this manuscript, the authors summarized the pathogenesis, genetic and environmental risk factors, high-risk population, and modern screening modalities for pancreatic cancer (PC), a deadly malignancy with limited treatment and screening methods. In general, the authors did a good job in reviewing the PC research field in both basic and clinical sides. Most up-to-date reference literatures are appropriately cited. The structure of this manuscript is well organized and relevant information is clearly conveyed to the audience. However, there are still some minor parts that could be included to make this manuscript more comprehensive.

1.      In section 2.3, when precursor lesions are introduced here, the authors only talked about PanIN lesions. Although PanIN is the majority one, Intraductal Papillary Mucinous Neoplasm (IPMN) and Mucinous Cystic Neoplasm (MCN) should also be introduced.

  2. In the same section 2.3, when acinar-to-ductal metaplasia (ADM) is introduced, only ANGPTL4 is described as a factor to influence this process. Actually, some other proteins, such as SOX9, KLF4/5, and ICAM-1 are also shown to regulate ADM formation and PDAC initiation. This information should be included in the text and Figure 1.

     3. In section 4.2.2, the authors introduced serum, urine, cerebrospinal fluid, or saliva as sources for liquid biopsy. Since this paper mainly focuses on PC, pancreatic juice and pancreatic cyst should be emphasized here, as they provide specific potential for PC diagnosis as liquid biopsy.

     4. There are totally four tables that are included in this manuscript. Table 1 is described in the text line 210 and table 3 is described in line 386. However, table 2 and table 4 are not described in the text. Therefore, it is a little confusing where these two tables should be appropriately inserted into the text. Similarly, figure 1 is not described in the text neither.

     5. There may be a formatting problem in Table 1, as there is no Function and Mutation effects information for 13q22.1. There is a typo in line 174. It should be TP53 instead of TP52.

Author Response

Pancreatic Tumorigenesis: Precursors, Genetic Risk Factors and Screening, [Current Oncology] Manuscript ID: curroncol-2004173

We would like to thank the learned reviewers and editor for consideration of our manuscript for publication and thoroughly appreciate the time taken to provide us with valuable comments to improve the readability and value of our contribution to literature. We have provided responses to all comments below.

The following issues have been addressed:

1. In section 2.3, when precursor lesions are introduced here, the authors only talked about PanIN lesions. Although PanIN is the majority one, Intraductal Papillary Mucinous Neoplasm (IPMN) and Mucinous Cystic Neoplasm (MCN) should also be introduced. In the same section 2.3, when acinar-to-ductal metaplasia (ADM) is introduced, only ANGPTL4 is described as a factor to influence this process. Actually, some other proteins, such as SOX9, KLF4/5, and ICAM-1 are also shown to regulate ADM formation and PDAC initiation. This information should be included in the text and Figure 1.

Authors’ response: We appreciate the detailed review of the pathogenesis for pancreatic cancer and have incorporated the highlighted processes in the text and figure.

1. In section 4.2.2, the authors introduced serum, urine, cerebrospinal fluid, or saliva as sources for liquid biopsy. Since this paper mainly focuses on PC, pancreatic juice and the pancreatic cyst should be emphasized here, as they provide the specific potential for PC diagnosis as liquid biopsy.

Authors’ response:  Thank you for pointing out this issue. We included a study demonstrating the utility of “liquid biopsy” for diagnosis when the findings from pathological examination are negative.

1. There are totally four tables that are included in this manuscript. Table 1 is described in the text line 210 and table 3 is described in line 386. However, table 2 and table 4 are not described in the text. Therefore, it is a little confusing where these two tables should be appropriately inserted into the text. Similarly, figure 1 is not described in the text neither.

Author’s response:  Thank you for bringing this to our attention. All the tables/figures are now referenced in the text.

4. There may be a formatting problem in Table 1, as there is no Function and Mutation effects information for 13q22.1. There is a typo in line 174. It should be TP53 instead of TP52

Authors’ response: The missing information has been added to the table, and the text was reviewed to ensure TP53 was spelled accurately.

Thank you 

The team 

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

This work makes an update on Precursors, Genetic Risk Factors and Screening for pancreatic cancer. The work is good and exhaustive in the treatment of these 3 aspects of pancreatic adenocarcinoma, especially item 4 (screening of pancreatic cancer) is very well developed and conceptually elaborated, including the tables located on lines 351 and 560.

Main observations:

Very important topics such as tumorigenesis and genetic factors need conceptual figures or tables that facilitate comprehensive reading.

They are: Items 2.3 (origin and precursors of pancreatic cancer), 3.1.1 (Familiar cancer syndromes) that contain 6 sub-items, and 3.1.2 (hereditary pancreatitis) especially deserve a scheme or figure that facilitates understanding. This latter is not only important because inflammation accelerates tumorigenesis but also because of its current prevalence.

Minor observations: Tables should have number and title.

Author Response

Authors’ response: We appreciate the reviewer’s insightful comments and agree that figures/tables would overall elevate the quality of the paper and facilitate complex concepts. We have added a figure that illustrates the pathogenesis of pancreatic cancer in a simplified manner. We have also summarized the different familial syndromes into a table that contains key information pertaining to each syndrome. 

Authors’ response: Thank you for highlighting this. Numbers and titles have been assigned to tables and figures.

Reviewer 2 Report

This is a good review of pancreatic cancer that recommends targeted screening of people with predisposing factors or a family history of the disease. I believe that it is a valuable aid to the clinicians in trying to diagnose people with pancreatic cancer at an early stage.

Author Response

Thank you for this comment. In addition, the whole manuscript was revised to correct any such errors and enhance readability.

Reviewer 3 Report

The manuscript is well written and well structured. The topic is interesting and in line with the journal.

The main question of this research is the summary of the current knowledge about the tumorogenesis and diagnosis of pancreatic cancer. The topic concludes several researches in the field of pancreatic cancer. It doesn't add anything new but thanks to this project you can find all the information in one place. The conclusion meets the main question. All the references are appropriate.

There are few minor errors, for example:

- line 60: "and the and the..."

- line 393: the sentence should probably start with CA242 not A242

Author Response

Authors' response: Thank you for pointing out the grammatical and spelling errors. The identified errors were rectified. In addition, the whole manuscript was revised to correct any such errors and enhance readability.