Reviewer's report
Title:Computational Prediction and Experimental Validation Associating FABP-1
and Pancreatic Adenocarcinoma with Diabetes
Version: 1Date:27 September 2010
Reviewer: Juergen Schrezenmeir
Reviewer's report:
The manuscript RN Sharaf et al. is interesting, but still has some draw backs
which require major compulsory revisions.
The methodology of search for candidates resulting in FABP1 should be
described more precisely to enable understanding the process of data analysis
and the results of this search should be given in detail to enable understanding
the basis of candidate selection. What was the scoring of FABP1 (between the
given range of +1.0 and -1.0) compared to other genes, what was the ranking
compared to other genes?
To further elucidate, whether diabetes may have been more or less likely to be
associated with FABP1 expression by tumor tissue, the duration of diabetes in
the 13 diabetes cases (based on patient’s histories) would be interesting to know.
Furthermore the grade of infiltration of the pancreas of the cases without
compared to the cases with diabetes would be of interest, since diabetes might
be due to the grade of infiltration, which may be related to the grade or kind of
differentiation (that may be related to FABP1 expression).
FABP1 is suggested to be involved in the pathogenesis of diabetes via facilitating
fat uptake, cellular trafficking, and chylomicron/VLDL production. This seems
unlikely to take place to a significant extent in pancreatic tumor tissue, which is
supplied by the nutrients via the portal vein. Therefore a secondary mechanism
should be suggested in case the findings may be confirmed in later studies.
Pg. 6
Which microarrays were used? (human genome wide? Which supplier?).
The authors state that a measure ranging from +1.0 (highest value found in
pathologic tissue) to -1.0 (lowest value in normal tissue) was used to rank the
genes expressed in diseased samples.
This score should be given in the results as well as the scores of the other 10
genes ranking close to (higher and/or lower than) FABP1.
It is confusing that this measure evidently was not used as stated, but a
comparison with pancreatitis and type 1 diabetes samples was used for
selection.
The sentence “we crossed the list” should be rephrased more precisely. Down to
which RR or OR was this “crossing” done?
Pg 7
The first sentence “given the beta cell …” is not clear.
Were all genes associated with DM or only those which were associated with
beta-cell function and insulin resistance in pancreatic carcinoma?
Why are type 2 diabetes susceptibility genes separately mentioned?
Pg 15
Last sentence: “to have”
Pg 16
Better rephrase:
“Only one pathologist scored immunohistochemistry. He, however, has several
years of experience.”
Table 1
The diabetes prevalence of 21% is in contrast to published data (45-65%). This
should be discussed by the authors.
Reviewer's report
Title:Computational Prediction and Experimental Validation Associating FABP-1
and Pancreatic Adenocarcinoma with Diabetes
Version: 1Date:27 September 2010
Reviewer: Juergen Schrezenmeir
Reviewer's report:
The manuscript RN Sharaf et al. is interesting, but still has some draw backs
which require major compulsory revisions.
The methodology of search for candidates resulting in FABP1 should be
described more precisely to enable understanding the process of data analysis
and the results of this search should be given in detail to enable understanding
the basis of candidate selection. What was the scoring of FABP1 (between the
given range of +1.0 and -1.0) compared to other genes, what was the ranking
compared to other genes?
To further elucidate, whether diabetes may have been more or less likely to be
associated with FABP1 expression by tumor tissue, the duration of diabetes in
the 13 diabetes cases (based on patient’s histories) would be interesting to know.
Furthermore the grade of infiltration of the pancreas of the cases without
compared to the cases with diabetes would be of interest, since diabetes might
be due to the grade of infiltration, which may be related to the grade or kind of
differentiation (that may be related to FABP1 expression).
FABP1 is suggested to be involved in the pathogenesis of diabetes via facilitating
fat uptake, cellular trafficking, and chylomicron/VLDL production. This seems
unlikely to take place to a significant extent in pancreatic tumor tissue, which is
supplied by the nutrients via the portal vein. Therefore a secondary mechanism
should be suggested in case the findings may be confirmed in later studies.
Pg. 6
Which microarrays were used? (human genome wide? Which supplier?).
The authors state that a measure ranging from +1.0 (highest value found in
pathologic tissue) to -1.0 (lowest value in normal tissue) was used to rank the
genes expressed in diseased samples.
This score should be given in the results as well as the scores of the other 10
genes ranking close to (higher and/or lower than) FABP1.
It is confusing that this measure evidently was not used as stated, but a
comparison with pancreatitis and type 1 diabetes samples was used for
selection.
The sentence “we crossed the list” should be rephrased more precisely. Down to
which RR or OR was this “crossing” done?
Pg 7
The first sentence “given the beta cell …” is not clear.
Were all genes associated with DM or only those which were associated with
beta-cell function and insulin resistance in pancreatic carcinoma?
Why are type 2 diabetes susceptibility genes separately mentioned?
Pg 15
Last sentence: “to have”
Pg 16
Better rephrase:
“Only one pathologist scored immunohistochemistry. He, however, has several
years of experience.”
Table 1
The diabetes prevalence of 21% is in contrast to published data (45-65%). This
should be discussed by the authors.
Please review this paper.
user
Reviewer's report
Title:Computational Prediction and Experimental Validation Associating FABP-1
and Pancreatic Adenocarcinoma with Diabetes
Version: 1Date:27 September 2010
Reviewer: Juergen Schrezenmeir
Reviewer's report:
The manuscript RN Sharaf et al. is interesting, but still has some draw backs
which require major compulsory revisions.
The methodology of search for candidates resulting in FABP1 should be
described more precisely to enable understanding the process of data analysis
and the results of this search should be given in detail to enable understanding
the basis of candidate selection. What was the scoring of FABP1 (between the
given range of +1.0 and -1.0) compared to other genes, what was the ranking
compared to other genes?
To further elucidate, whether diabetes may have been more or less likely to be
associated with FABP1 expression by tumor tissue, the duration of diabetes in
the 13 diabetes cases (based on patient’s histories) would be interesting to know.
Furthermore the grade of infiltration of the pancreas of the cases without
compared to the cases with diabetes would be of interest, since diabetes might
be due to the grade of infiltration, which may be related to the grade or kind of
differentiation (that may be related to FABP1 expression).
FABP1 is suggested to be involved in the pathogenesis of diabetes via facilitating
fat uptake, cellular trafficking, and chylomicron/VLDL production. This seems
unlikely to take place to a significant extent in pancreatic tumor tissue, which is
supplied by the nutrients via the portal vein. Therefore a secondary mechanism
should be suggested in case the findings may be confirmed in later studies.
Pg. 6
Which microarrays were used? (human genome wide? Which supplier?).
The authors state that a measure ranging from +1.0 (highest value found in
pathologic tissue) to -1.0 (lowest value in normal tissue) was used to rank the
genes expressed in diseased samples.
This score should be given in the results as well as the scores of the other 10
genes ranking close to (higher and/or lower than) FABP1.
It is confusing that this measure evidently was not used as stated, but a
comparison with pancreatitis and type 1 diabetes samples was used for
selection.
The sentence “we crossed the list” should be rephrased more precisely. Down to
which RR or OR was this “crossing” done?
Pg 7
The first sentence “given the beta cell …” is not clear.
Were all genes associated with DM or only those which were associated with
beta-cell function and insulin resistance in pancreatic carcinoma?
Why are type 2 diabetes susceptibility genes separately mentioned?
Pg 15
Last sentence: “to have”
Pg 16
Better rephrase:
“Only one pathologist scored immunohistochemistry. He, however, has several
years of experience.”
Table 1
The diabetes prevalence of 21% is in contrast to published data (45-65%). This
should be discussed by the authors.
assistant