Reviewer's report
Title:Computational Prediction and Experimental Validation Associating FABP-1
and Pancreatic Adenocarcinoma with Diabetes
Version: 1Date:31 August 2010
Reviewer: David Morse
Reviewer's report:
The article uses a previously reported database containing human
disease-related expression changes generated from publicly available DNA
microarray data to initally identify a set of genes with increased expression in
pancreatic cancer compared to expression in acute pancreatitis and type I
diabetes mellitus (DM). The list was then filtered using a list of genes known to
be genetically associated with DM. The resulting list was again filtered for a
biofluid database containing proteins know to be detected in blood or urine. This
is a thorough, well presented study demonstrating the potential for this approach
to identify useful diagnostic markers for pancreatic adenocarcinoma associated
with diabetes. However, the potential utility for FABP-1 as a diagnostic marker is
questionable (as detailed below).
Major Essential Revisions:
1) Although FABP-1 is expressed in renal proximal tubule cells which shed into
the urine, it is doubtful that cells from PaC will also shed into the urine by this
mechanism. However, circulating tumor cells (CTCs) in the blood have been
found to express FABP-1 after enriching the sample for CTCs extracting and
detecting FABP-1 mRNA, and has thus been proposed as a marker for CTCs
(study not-referenced in the manuscript). Unfortunately, CTCs are only
associated with metastatic disease and thus could only be used for diagnosis of
advanced stages of cancer. Otherwise, being that FABP-1 is cytoplasmic and not
found on the cell-surface, it is difficult to see the utility of FABP-1 as a diagnostic
marker because it would be difficult to develop a targeted imaging probe against
it. The authors should more clearly state/justify the proposed method that will be
used for detection of this diagnostic marker in patients.
Minor Essential Revisions:
2) Figure 2 would be better presented in the results section.
3) Page 12, 3rd paragraph - There is a typo, FABP1-1 should be FABP-1.
Discretionary revisions:
4) Based on the representative images provided for Figure 2, a score of 1
represents weak staining (expression). Hence, only 20% of ‘PaC-DM’, 10% of all
‘PaC’ and 5% of ‘PaC no DM’ have moderate to strong expression of FABP-1.
Since it is not clear that weak expression could be detected relative to expression
in normal tissues in the blood or urine, the reported 50% expression of FABP-1 in
PaC-DM possibly overstates the potential for diagnostic utility (although 20%
coverage is not bad). As reported, this marker is not an absolute marker of
diabetes associated pancreatic cancer, e.g. 5% of PaC with no DM moderately or
strongly express this marker. Based on these numbers, 4 out of 5 (80%) of
tumors expressing this marker will have associated DM (which is not bad). The
authors may choose to use a more stringent, and thus more relevant, cutoff for
IHC data when reporting the percentage of tumors covered by the FABP-1
marker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Computational Prediction and Experimental Validation Associating FABP-1
and Pancreatic Adenocarcinoma with Diabetes
Version: 1Date:31 August 2010
Reviewer: David Morse
Reviewer's report:
The article uses a previously reported database containing human
disease-related expression changes generated from publicly available DNA
microarray data to initally identify a set of genes with increased expression in
pancreatic cancer compared to expression in acute pancreatitis and type I
diabetes mellitus (DM). The list was then filtered using a list of genes known to
be genetically associated with DM. The resulting list was again filtered for a
biofluid database containing proteins know to be detected in blood or urine. This
is a thorough, well presented study demonstrating the potential for this approach
to identify useful diagnostic markers for pancreatic adenocarcinoma associated
with diabetes. However, the potential utility for FABP-1 as a diagnostic marker is
questionable (as detailed below).
Major Essential Revisions:
1) Although FABP-1 is expressed in renal proximal tubule cells which shed into
the urine, it is doubtful that cells from PaC will also shed into the urine by this
mechanism. However, circulating tumor cells (CTCs) in the blood have been
found to express FABP-1 after enriching the sample for CTCs extracting and
detecting FABP-1 mRNA, and has thus been proposed as a marker for CTCs
(study not-referenced in the manuscript). Unfortunately, CTCs are only
associated with metastatic disease and thus could only be used for diagnosis of
advanced stages of cancer. Otherwise, being that FABP-1 is cytoplasmic and not
found on the cell-surface, it is difficult to see the utility of FABP-1 as a diagnostic
marker because it would be difficult to develop a targeted imaging probe against
it. The authors should more clearly state/justify the proposed method that will be
used for detection of this diagnostic marker in patients.
Minor Essential Revisions:
2) Figure 2 would be better presented in the results section.
3) Page 12, 3rd paragraph - There is a typo, FABP1-1 should be FABP-1.
Discretionary revisions:
4) Based on the representative images provided for Figure 2, a score of 1
represents weak staining (expression). Hence, only 20% of ‘PaC-DM’, 10% of all
‘PaC’ and 5% of ‘PaC no DM’ have moderate to strong expression of FABP-1.
Since it is not clear that weak expression could be detected relative to expression
in normal tissues in the blood or urine, the reported 50% expression of FABP-1 in
PaC-DM possibly overstates the potential for diagnostic utility (although 20%
coverage is not bad). As reported, this marker is not an absolute marker of
diabetes associated pancreatic cancer, e.g. 5% of PaC with no DM moderately or
strongly express this marker. Based on these numbers, 4 out of 5 (80%) of
tumors expressing this marker will have associated DM (which is not bad). The
authors may choose to use a more stringent, and thus more relevant, cutoff for
IHC data when reporting the percentage of tumors covered by the FABP-1
marker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Computational Prediction and Experimental Validation Associating FABP-1
and Pancreatic Adenocarcinoma with Diabetes
Version: 1Date:31 August 2010
Reviewer: David Morse
Reviewer's report:
The article uses a previously reported database containing human
disease-related expression changes generated from publicly available DNA
microarray data to initally identify a set of genes with increased expression in
pancreatic cancer compared to expression in acute pancreatitis and type I
diabetes mellitus (DM). The list was then filtered using a list of genes known to
be genetically associated with DM. The resulting list was again filtered for a
biofluid database containing proteins know to be detected in blood or urine. This
is a thorough, well presented study demonstrating the potential for this approach
to identify useful diagnostic markers for pancreatic adenocarcinoma associated
with diabetes. However, the potential utility for FABP-1 as a diagnostic marker is
questionable (as detailed below).
Major Essential Revisions:
1) Although FABP-1 is expressed in renal proximal tubule cells which shed into
the urine, it is doubtful that cells from PaC will also shed into the urine by this
mechanism. However, circulating tumor cells (CTCs) in the blood have been
found to express FABP-1 after enriching the sample for CTCs extracting and
detecting FABP-1 mRNA, and has thus been proposed as a marker for CTCs
(study not-referenced in the manuscript). Unfortunately, CTCs are only
associated with metastatic disease and thus could only be used for diagnosis of
advanced stages of cancer. Otherwise, being that FABP-1 is cytoplasmic and not
found on the cell-surface, it is difficult to see the utility of FABP-1 as a diagnostic
marker because it would be difficult to develop a targeted imaging probe against
it. The authors should more clearly state/justify the proposed method that will be
used for detection of this diagnostic marker in patients.
Minor Essential Revisions:
2) Figure 2 would be better presented in the results section.
3) Page 12, 3rd paragraph - There is a typo, FABP1-1 should be FABP-1.
Discretionary revisions:
4) Based on the representative images provided for Figure 2, a score of 1
represents weak staining (expression). Hence, only 20% of ‘PaC-DM’, 10% of all
‘PaC’ and 5% of ‘PaC no DM’ have moderate to strong expression of FABP-1.
Since it is not clear that weak expression could be detected relative to expression
in normal tissues in the blood or urine, the reported 50% expression of FABP-1 in
PaC-DM possibly overstates the potential for diagnostic utility (although 20%
coverage is not bad). As reported, this marker is not an absolute marker of
diabetes associated pancreatic cancer, e.g. 5% of PaC with no DM moderately or
strongly express this marker. Based on these numbers, 4 out of 5 (80%) of
tumors expressing this marker will have associated DM (which is not bad). The
authors may choose to use a more stringent, and thus more relevant, cutoff for
IHC data when reporting the percentage of tumors covered by the FABP-1
marker.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
assistant