Reviewer's report
Title:Activation of Liver FGF21 in Hepatocarcinogenesis and During Hepatic
Stress
Version: 2Date:15 January 2013
Reviewer: Toshnari Takamura
Reviewer's report:
Yang et al. have reported up-regulation of hepatic expression of FGF21 in
response to possible stress associated with carcinogenesis from observation in
cultured cell, mice and human samples. Although they report various disease
conditions leading to upregulation of FGF21, most of these findings are not novel
and seem still phenomenological. Their data do not support their conclusion that
seems over-stated from incomplete data. The following points should be
improved before accept for publication.
Major points
1. Most of the stimuli leading to FGF21 presented are already known. However,
the finding that loss of p53 upregulates hepatic expression of FGF21 seems to
be novel. Therefore, authors should investigate whether p53 binds to or
competes with specific area in the FGF21 gene promoter by using a ChIP assay
or gel shift assay.
2. Is p53 dysfunction associated with hepatic stresses during carcinogenesis,
such as PHx, DEN, or loss of loss of SAV1, MST1/MST2 or PTEN, that
upregulate hepatic expression of FGF21?
3. Although authors show representative pictures of FGF21 staining in Fig. 5 and
6, some exceptions seem to exist as authors explained in the result section. For
example, some normal liver sections were positive in FGF21. If authors propose
diagnostic significance of FGF21 in various stress conditions in the liver
diseases, authors at least should summarize in the table the positivity rate of
FGF21 staining in each disease condition.
4. Because immunohistochemistry lacks quantitative significance, blood levels of
FGF21 in various liver diseases are needed together with immunohistochemical
analyses of FGF21 in the liver sections for their conclusion.
5. It has recently been reported that impairment of mitochondrial respiratory
chain by its inhibitors or autophagy deficiency induces FGF21 both in the liver
and skeletal muscle. Authors should address this finding in relation to their data.
6. It seems difficult for non-pathologists to understand the immunohistochemistry
data of FGF21 staining in Fig. 5 and 6. Authors should assist readers
understand, for example, the border between tumor and non-tumor area.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no conflicts of interest relating to this paper.
Reviewer's report
Title:Activation of Liver FGF21 in Hepatocarcinogenesis and During Hepatic
Stress
Version: 2Date:15 January 2013
Reviewer: Toshnari Takamura
Reviewer's report:
Yang et al. have reported up-regulation of hepatic expression of FGF21 in
response to possible stress associated with carcinogenesis from observation in
cultured cell, mice and human samples. Although they report various disease
conditions leading to upregulation of FGF21, most of these findings are not novel
and seem still phenomenological. Their data do not support their conclusion that
seems over-stated from incomplete data. The following points should be
improved before accept for publication.
Major points
1. Most of the stimuli leading to FGF21 presented are already known. However,
the finding that loss of p53 upregulates hepatic expression of FGF21 seems to
be novel. Therefore, authors should investigate whether p53 binds to or
competes with specific area in the FGF21 gene promoter by using a ChIP assay
or gel shift assay.
2. Is p53 dysfunction associated with hepatic stresses during carcinogenesis,
such as PHx, DEN, or loss of loss of SAV1, MST1/MST2 or PTEN, that
upregulate hepatic expression of FGF21?
3. Although authors show representative pictures of FGF21 staining in Fig. 5 and
6, some exceptions seem to exist as authors explained in the result section. For
example, some normal liver sections were positive in FGF21. If authors propose
diagnostic significance of FGF21 in various stress conditions in the liver
diseases, authors at least should summarize in the table the positivity rate of
FGF21 staining in each disease condition.
4. Because immunohistochemistry lacks quantitative significance, blood levels of
FGF21 in various liver diseases are needed together with immunohistochemical
analyses of FGF21 in the liver sections for their conclusion.
5. It has recently been reported that impairment of mitochondrial respiratory
chain by its inhibitors or autophagy deficiency induces FGF21 both in the liver
and skeletal muscle. Authors should address this finding in relation to their data.
6. It seems difficult for non-pathologists to understand the immunohistochemistry
data of FGF21 staining in Fig. 5 and 6. Authors should assist readers
understand, for example, the border between tumor and non-tumor area.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no conflicts of interest relating to this paper.
Please review this paper.
user
Reviewer's report
Title:Activation of Liver FGF21 in Hepatocarcinogenesis and During Hepatic
Stress
Version: 2Date:15 January 2013
Reviewer: Toshnari Takamura
Reviewer's report:
Yang et al. have reported up-regulation of hepatic expression of FGF21 in
response to possible stress associated with carcinogenesis from observation in
cultured cell, mice and human samples. Although they report various disease
conditions leading to upregulation of FGF21, most of these findings are not novel
and seem still phenomenological. Their data do not support their conclusion that
seems over-stated from incomplete data. The following points should be
improved before accept for publication.
Major points
1. Most of the stimuli leading to FGF21 presented are already known. However,
the finding that loss of p53 upregulates hepatic expression of FGF21 seems to
be novel. Therefore, authors should investigate whether p53 binds to or
competes with specific area in the FGF21 gene promoter by using a ChIP assay
or gel shift assay.
2. Is p53 dysfunction associated with hepatic stresses during carcinogenesis,
such as PHx, DEN, or loss of loss of SAV1, MST1/MST2 or PTEN, that
upregulate hepatic expression of FGF21?
3. Although authors show representative pictures of FGF21 staining in Fig. 5 and
6, some exceptions seem to exist as authors explained in the result section. For
example, some normal liver sections were positive in FGF21. If authors propose
diagnostic significance of FGF21 in various stress conditions in the liver
diseases, authors at least should summarize in the table the positivity rate of
FGF21 staining in each disease condition.
4. Because immunohistochemistry lacks quantitative significance, blood levels of
FGF21 in various liver diseases are needed together with immunohistochemical
analyses of FGF21 in the liver sections for their conclusion.
5. It has recently been reported that impairment of mitochondrial respiratory
chain by its inhibitors or autophagy deficiency induces FGF21 both in the liver
and skeletal muscle. Authors should address this finding in relation to their data.
6. It seems difficult for non-pathologists to understand the immunohistochemistry
data of FGF21 staining in Fig. 5 and 6. Authors should assist readers
understand, for example, the border between tumor and non-tumor area.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I have no conflicts of interest relating to this paper.
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