Reviewer’s report
Title: 
Evaluation of serum ATX and LPA as potential diagnostic biomarkers in
patients with pancreatic cancer
Version: 
1 
Date: 
17 Oct 2019
Reviewer's report:
This is an interesting study comparing the levels of three serum markers, ATX,
LPA and CA 19-9, in pancreatic cancer (PC) patients prior to treatment, in
healthy volunteers, and in benign pancreatic disease patients. 
The serum marker
CA 19-9 is well known, therefore ATX and LPA were considered alone or in
combination with CA 19-9 to distinguish early phase and/or late phase pancreatic
cancer patients from healthy controls or benign disease patients. 
Table 1
provided patient demographics, while Table 2 provided basic lab test values,
which was not really necessary (just demonstrates that these tests are not
diagnostic for PC, which is well known). 
Table 3 compared each marker alone in
the various patient groups, which showed that LPA was a less reliable marker
than CA19-9. Table 4 combined markers. The study's statistical analysis seems
sound, but this is not an area of expertise for me and additional statistical review
would be helpful. 
The authors concluded that neither ATX nor LPA alone gave better sensitivity
and specificity than CA19-9 to distinguish early phase pancreatic cancer from
benign disease or from non-cancer patients. 
This is critical since early detection
is the gold standard for cancer biomarkers. 
The ability to detect late stage disease
is less relevant, as other factors can be used to diagnose PC in later stages.
However, when all three markers were considered together, the study
demonstrated that these three markers could improve early detection of
pancreatic cancer over CA19-9 alone, and thus may have clinical utility for Stage
1 and 2 disease. 
The image quality of Figure 1 was very poor, and it was hard to
assess how much it added to the manuscript.
This study was well done but brief. 
It was a short communication type of paper,
not a substantial research article. 
The conclusions were sound, and the
limitations of the study, particularly the limited patient diversity, were noted.
The authors seemed to try to make the paper longer by repeating background and
methods in the discussion section (pages 12-14) - this is not discussion material
and should be removed. 
As the scope of the study is small, one thought would be
to assess these serum markers after treatment to determine if their levels track
with response to treatment.
In summary, this is a good but very limited study. 
It would probably be best as
as a short communication and not a full research article.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
I agree to the open peer review policy of the journal. I understand that my name
will be included on my report to the authors and, if the manuscript is accepted
for publication, my named report including any attachments I upload will be
posted on the website along with the authors' responses. I agree for my report to
be made available under an Open Access Creative Commons CC-BY license
(
http://creativecommons.org/licenses/by/4.0/
). I understand that any comments
which I do not wish to be included in my named report can be included as
confidential comments to the editors, which will not be published.
I agree to the open peer review policy of the journal
Reviewer’s report
Title: 
Evaluation of serum ATX and LPA as potential diagnostic biomarkers in
patients with pancreatic cancer
Version: 
1 
Date: 
17 Oct 2019
Reviewer's report:
This is an interesting study comparing the levels of three serum markers, ATX,
LPA and CA 19-9, in pancreatic cancer (PC) patients prior to treatment, in
healthy volunteers, and in benign pancreatic disease patients. 
The serum marker
CA 19-9 is well known, therefore ATX and LPA were considered alone or in
combination with CA 19-9 to distinguish early phase and/or late phase pancreatic
cancer patients from healthy controls or benign disease patients. 
Table 1
provided patient demographics, while Table 2 provided basic lab test values,
which was not really necessary (just demonstrates that these tests are not
diagnostic for PC, which is well known). 
Table 3 compared each marker alone in
the various patient groups, which showed that LPA was a less reliable marker
than CA19-9. Table 4 combined markers. The study's statistical analysis seems
sound, but this is not an area of expertise for me and additional statistical review
would be helpful. 
The authors concluded that neither ATX nor LPA alone gave better sensitivity
and specificity than CA19-9 to distinguish early phase pancreatic cancer from
benign disease or from non-cancer patients. 
This is critical since early detection
is the gold standard for cancer biomarkers. 
The ability to detect late stage disease
is less relevant, as other factors can be used to diagnose PC in later stages.
However, when all three markers were considered together, the study
demonstrated that these three markers could improve early detection of
pancreatic cancer over CA19-9 alone, and thus may have clinical utility for Stage
1 and 2 disease. 
The image quality of Figure 1 was very poor, and it was hard to
assess how much it added to the manuscript.
This study was well done but brief. 
It was a short communication type of paper,
not a substantial research article. 
The conclusions were sound, and the
limitations of the study, particularly the limited patient diversity, were noted.
The authors seemed to try to make the paper longer by repeating background and
methods in the discussion section (pages 12-14) - this is not discussion material
and should be removed. 
As the scope of the study is small, one thought would be
to assess these serum markers after treatment to determine if their levels track
with response to treatment.
In summary, this is a good but very limited study. 
It would probably be best as
as a short communication and not a full research article.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
I agree to the open peer review policy of the journal. I understand that my name
will be included on my report to the authors and, if the manuscript is accepted
for publication, my named report including any attachments I upload will be
posted on the website along with the authors' responses. I agree for my report to
be made available under an Open Access Creative Commons CC-BY license
(
http://creativecommons.org/licenses/by/4.0/
). I understand that any comments
which I do not wish to be included in my named report can be included as
confidential comments to the editors, which will not be published.
I agree to the open peer review policy of the journal
Please review this paper.
user
Reviewer’s report
Title: 
Evaluation of serum ATX and LPA as potential diagnostic biomarkers in
patients with pancreatic cancer
Version: 
1 
Date: 
17 Oct 2019
Reviewer's report:
This is an interesting study comparing the levels of three serum markers, ATX,
LPA and CA 19-9, in pancreatic cancer (PC) patients prior to treatment, in
healthy volunteers, and in benign pancreatic disease patients. 
The serum marker
CA 19-9 is well known, therefore ATX and LPA were considered alone or in
combination with CA 19-9 to distinguish early phase and/or late phase pancreatic
cancer patients from healthy controls or benign disease patients. 
Table 1
provided patient demographics, while Table 2 provided basic lab test values,
which was not really necessary (just demonstrates that these tests are not
diagnostic for PC, which is well known). 
Table 3 compared each marker alone in
the various patient groups, which showed that LPA was a less reliable marker
than CA19-9. Table 4 combined markers. The study's statistical analysis seems
sound, but this is not an area of expertise for me and additional statistical review
would be helpful. 
The authors concluded that neither ATX nor LPA alone gave better sensitivity
and specificity than CA19-9 to distinguish early phase pancreatic cancer from
benign disease or from non-cancer patients. 
This is critical since early detection
is the gold standard for cancer biomarkers. 
The ability to detect late stage disease
is less relevant, as other factors can be used to diagnose PC in later stages.
However, when all three markers were considered together, the study
demonstrated that these three markers could improve early detection of
pancreatic cancer over CA19-9 alone, and thus may have clinical utility for Stage
1 and 2 disease. 
The image quality of Figure 1 was very poor, and it was hard to
assess how much it added to the manuscript.
This study was well done but brief. 
It was a short communication type of paper,
not a substantial research article. 
The conclusions were sound, and the
limitations of the study, particularly the limited patient diversity, were noted.
The authors seemed to try to make the paper longer by repeating background and
methods in the discussion section (pages 12-14) - this is not discussion material
and should be removed. 
As the scope of the study is small, one thought would be
to assess these serum markers after treatment to determine if their levels track
with response to treatment.
In summary, this is a good but very limited study. 
It would probably be best as
as a short communication and not a full research article.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the
authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
Are you able to assess any statistics in the manuscript or would you
recommend an additional statistical review?
If an additional statistical review is recommended, please specify what aspects
require further assessment in your comments to the editors.
I recommend additional statistical review
Quality of written English
Please indicate the quality of language in the manuscript:
Acceptable
Declaration of competing interests
Please complete a declaration of competing interests, considering the following
questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
I agree to the open peer review policy of the journal. I understand that my name
will be included on my report to the authors and, if the manuscript is accepted
for publication, my named report including any attachments I upload will be
posted on the website along with the authors' responses. I agree for my report to
be made available under an Open Access Creative Commons CC-BY license
(
http://creativecommons.org/licenses/by/4.0/
). I understand that any comments
which I do not wish to be included in my named report can be included as
confidential comments to the editors, which will not be published.
I agree to the open peer review policy of the journal
assistant