Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:20 November 2014
Reviewer: cedric le may
Reviewer's report:
In this study, Bhat M. and colleagues have compared PCSK9 expression levels
in hepatocelular carcinoma (HCC) and adjacent hepatic tissues.
Using immunohistochemistry, they observed that PCSK9 staining was
significantly less expressed in HCC compared to adjacent tissues. Furthermore,
PCSK9 staining was not correlated to the grade of tumor but did significantly
correlate with the stage of fibrosis. Unfortunately, these interesting finding was
poorly validated by quantitative real time PCR. Indeed, the authors only observed
a trend for a decreased PCSK9 expression in HCC compared to adjacent
tissues. Finally they did quantify circulating PCSK9 by ELISA in patients with
HCC and control patients without HCC. They reported that serum PCSK9 levels
were significantly increased among patients with HCC compared to control
patients.
In absence of LDLr staining or LDLr protein quantification in HCC or adjacent
tissues, it is difficult to evaluate and extrapolate the functional and physiological
relevance of these findings.
It is crucial to further explore the putative link between PCSK9 and HCC
regarding the development of PCSK9 inhibitors. However, the data presented in
the actual manuscript are to date insufficent.
Major Compulsory Revisions
1. The strongest data have been obtained from immunohistochemistry, it would
be important to reinforce the quantification by adding representative pictures from
HCC and control tissues stained for PCSK9.
2. A western-blot analysis of PCSK9 in HCC and HCC tissues should be added
to validate the immunostaining experiments.
3. Finally, as PCSK9 expression is reduced in HCC but the circulating PCSK9
levels is increased in HCC patients compared to non HCC control patients, it is
necessary to measure in HCC the real effect on cell surface LDLr. Thus, it is
required to quantified by immunohistochemitry and western blot the LDLr protein
levels in HCC and ajdjacent tissues.
Minor Essential Revisions
1. The authors should precise whether patients included in the study received
any pharmacological treatment.
Level of interest: An article whose findings are important to those with closely
related research interests
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.
Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:20 November 2014
Reviewer: cedric le may
Reviewer's report:
In this study, Bhat M. and colleagues have compared PCSK9 expression levels
in hepatocelular carcinoma (HCC) and adjacent hepatic tissues.
Using immunohistochemistry, they observed that PCSK9 staining was
significantly less expressed in HCC compared to adjacent tissues. Furthermore,
PCSK9 staining was not correlated to the grade of tumor but did significantly
correlate with the stage of fibrosis. Unfortunately, these interesting finding was
poorly validated by quantitative real time PCR. Indeed, the authors only observed
a trend for a decreased PCSK9 expression in HCC compared to adjacent
tissues. Finally they did quantify circulating PCSK9 by ELISA in patients with
HCC and control patients without HCC. They reported that serum PCSK9 levels
were significantly increased among patients with HCC compared to control
patients.
In absence of LDLr staining or LDLr protein quantification in HCC or adjacent
tissues, it is difficult to evaluate and extrapolate the functional and physiological
relevance of these findings.
It is crucial to further explore the putative link between PCSK9 and HCC
regarding the development of PCSK9 inhibitors. However, the data presented in
the actual manuscript are to date insufficent.
Major Compulsory Revisions
1. The strongest data have been obtained from immunohistochemistry, it would
be important to reinforce the quantification by adding representative pictures from
HCC and control tissues stained for PCSK9.
2. A western-blot analysis of PCSK9 in HCC and HCC tissues should be added
to validate the immunostaining experiments.
3. Finally, as PCSK9 expression is reduced in HCC but the circulating PCSK9
levels is increased in HCC patients compared to non HCC control patients, it is
necessary to measure in HCC the real effect on cell surface LDLr. Thus, it is
required to quantified by immunohistochemitry and western blot the LDLr protein
levels in HCC and ajdjacent tissues.
Minor Essential Revisions
1. The authors should precise whether patients included in the study received
any pharmacological treatment.
Level of interest: An article whose findings are important to those with closely
related research interests
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.
Please review this paper.
user
Reviewer's report
Title:Decreased PCSK9 expression in human Hepatocellular Carcinoma
Version:2Date:20 November 2014
Reviewer: cedric le may
Reviewer's report:
In this study, Bhat M. and colleagues have compared PCSK9 expression levels
in hepatocelular carcinoma (HCC) and adjacent hepatic tissues.
Using immunohistochemistry, they observed that PCSK9 staining was
significantly less expressed in HCC compared to adjacent tissues. Furthermore,
PCSK9 staining was not correlated to the grade of tumor but did significantly
correlate with the stage of fibrosis. Unfortunately, these interesting finding was
poorly validated by quantitative real time PCR. Indeed, the authors only observed
a trend for a decreased PCSK9 expression in HCC compared to adjacent
tissues. Finally they did quantify circulating PCSK9 by ELISA in patients with
HCC and control patients without HCC. They reported that serum PCSK9 levels
were significantly increased among patients with HCC compared to control
patients.
In absence of LDLr staining or LDLr protein quantification in HCC or adjacent
tissues, it is difficult to evaluate and extrapolate the functional and physiological
relevance of these findings.
It is crucial to further explore the putative link between PCSK9 and HCC
regarding the development of PCSK9 inhibitors. However, the data presented in
the actual manuscript are to date insufficent.
Major Compulsory Revisions
1. The strongest data have been obtained from immunohistochemistry, it would
be important to reinforce the quantification by adding representative pictures from
HCC and control tissues stained for PCSK9.
2. A western-blot analysis of PCSK9 in HCC and HCC tissues should be added
to validate the immunostaining experiments.
3. Finally, as PCSK9 expression is reduced in HCC but the circulating PCSK9
levels is increased in HCC patients compared to non HCC control patients, it is
necessary to measure in HCC the real effect on cell surface LDLr. Thus, it is
required to quantified by immunohistochemitry and western blot the LDLr protein
levels in HCC and ajdjacent tissues.
Minor Essential Revisions
1. The authors should precise whether patients included in the study received
any pharmacological treatment.
Level of interest: An article whose findings are important to those with closely
related research interests
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.
assistant