Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:30 November 2014
Reviewer: Bertrand Cariou
Reviewer's report:
In this article, Bhat et al adressed an important question concerning the potential
link between PCSK9 and liver carcinogenesis. Some preclinical data in mouse
suggest that PCSK9 could play a role in liver regeneration and potentially
carcinogenesis. However, there is no data available in humans yet.
Unfortunately, the data presented here don't support the extensive conclusions
drawn by the authors.
Major Revisions:
1. Concerning the immunohistochemistry data, some controls are lacking.
Indeed, the authors only compared PCSK9 expression in HCC and in adjacent
cirrhotic liver. What is the expression of PCSK9 in normal liver? At this time, it
remains unclear whether PCSK9 is downregulated in HCC or overexpressed in
fibrotic liver?
2. The patients are heterogeneous with a mix of hepatitis B & C, NASH, alcoholic
cirrhosis, etc...It should be remind here that it has been suggested that PCSK9
can play a role in the pathophysiology of hepatitis C by controlling the expression
of some specific receptors involved in the uptake of the viruses (LDL-R, CD81).
The authors shoudl perfomed a regression analysis to determine whteher the
etiology of liver disease alters the results of PCSK9 expression in HCC.
3. It's a pity that plasma PCSK9 levels were not measured in the same
population than those for PCSK9 expression in HCC. The number of controls is
very small...What are the clincial characteristics (etiology of liver disease) of the
patients?
4. Since it has been demonstrated that the effect of PCSK9 in liver regeneration
is dependent of cholesterol intake in mice, the plasma lipid parameters of the
studied patients for PCSK9 expression analyses must be described.
Minor points:
1. The quality of the figure 2 is poor
2. For Q-PCR analyses, more than only 1 house-keeping (18S) gene must be
used.
3. The discussion is very speculative (notably concerning the link between
PCSK9 and LDL-R expression, in the absence of LDL-R expression data....)
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests below.
Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:30 November 2014
Reviewer: Bertrand Cariou
Reviewer's report:
In this article, Bhat et al adressed an important question concerning the potential
link between PCSK9 and liver carcinogenesis. Some preclinical data in mouse
suggest that PCSK9 could play a role in liver regeneration and potentially
carcinogenesis. However, there is no data available in humans yet.
Unfortunately, the data presented here don't support the extensive conclusions
drawn by the authors.
Major Revisions:
1. Concerning the immunohistochemistry data, some controls are lacking.
Indeed, the authors only compared PCSK9 expression in HCC and in adjacent
cirrhotic liver. What is the expression of PCSK9 in normal liver? At this time, it
remains unclear whether PCSK9 is downregulated in HCC or overexpressed in
fibrotic liver?
2. The patients are heterogeneous with a mix of hepatitis B & C, NASH, alcoholic
cirrhosis, etc...It should be remind here that it has been suggested that PCSK9
can play a role in the pathophysiology of hepatitis C by controlling the expression
of some specific receptors involved in the uptake of the viruses (LDL-R, CD81).
The authors shoudl perfomed a regression analysis to determine whteher the
etiology of liver disease alters the results of PCSK9 expression in HCC.
3. It's a pity that plasma PCSK9 levels were not measured in the same
population than those for PCSK9 expression in HCC. The number of controls is
very small...What are the clincial characteristics (etiology of liver disease) of the
patients?
4. Since it has been demonstrated that the effect of PCSK9 in liver regeneration
is dependent of cholesterol intake in mice, the plasma lipid parameters of the
studied patients for PCSK9 expression analyses must be described.
Minor points:
1. The quality of the figure 2 is poor
2. For Q-PCR analyses, more than only 1 house-keeping (18S) gene must be
used.
3. The discussion is very speculative (notably concerning the link between
PCSK9 and LDL-R expression, in the absence of LDL-R expression data....)
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests below.
Please review this paper.
user
Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:30 November 2014
Reviewer: Bertrand Cariou
Reviewer's report:
In this article, Bhat et al adressed an important question concerning the potential
link between PCSK9 and liver carcinogenesis. Some preclinical data in mouse
suggest that PCSK9 could play a role in liver regeneration and potentially
carcinogenesis. However, there is no data available in humans yet.
Unfortunately, the data presented here don't support the extensive conclusions
drawn by the authors.
Major Revisions:
1. Concerning the immunohistochemistry data, some controls are lacking.
Indeed, the authors only compared PCSK9 expression in HCC and in adjacent
cirrhotic liver. What is the expression of PCSK9 in normal liver? At this time, it
remains unclear whether PCSK9 is downregulated in HCC or overexpressed in
fibrotic liver?
2. The patients are heterogeneous with a mix of hepatitis B & C, NASH, alcoholic
cirrhosis, etc...It should be remind here that it has been suggested that PCSK9
can play a role in the pathophysiology of hepatitis C by controlling the expression
of some specific receptors involved in the uptake of the viruses (LDL-R, CD81).
The authors shoudl perfomed a regression analysis to determine whteher the
etiology of liver disease alters the results of PCSK9 expression in HCC.
3. It's a pity that plasma PCSK9 levels were not measured in the same
population than those for PCSK9 expression in HCC. The number of controls is
very small...What are the clincial characteristics (etiology of liver disease) of the
patients?
4. Since it has been demonstrated that the effect of PCSK9 in liver regeneration
is dependent of cholesterol intake in mice, the plasma lipid parameters of the
studied patients for PCSK9 expression analyses must be described.
Minor points:
1. The quality of the figure 2 is poor
2. For Q-PCR analyses, more than only 1 house-keeping (18S) gene must be
used.
3. The discussion is very speculative (notably concerning the link between
PCSK9 and LDL-R expression, in the absence of LDL-R expression data....)
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests below.
assistant