Title: A meta-analysis of the prognostic impact of tissue Golgi protein 73(tGP73) in
hepatocellular carcinoma
Version: 1 Date: 15 Oct 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This manuscript describes a meta-analysis of studies investigating
the beneficial use of liver tissue-expressed GP73 as a prognostic marker for liver cancer. My
overall impression is that this study is mainly confirmatory of other recently published meta-
analyses involving liver disease and serum GP73 (2 alone this year), however, as far as I
know, no meta-analysis focussing on tissue-expressed GP73 has been published so far. The
methodology used by the authors is based on the Cochrane Review manager and data analysis
software. The authors identified 12 datasets from 10 studies. All expected parameters are well
described and fully disclosed, including the PRISM chart, appropriate dataset description, and
outputs. The study does meet best practice. While the study cohort is quite small for this type of
analysis, the methodology is valid and applied appropriately. The only criticism I have is that
there are some discrepancies in the text that need addressing, as well as English language editing.
This study has its merits, though solely on the grounds that a meta-analysis of tissue expressed
GP73 associated with hepatocellular carcinoma has not been published so far. However, one
could argue that serum GP73 has been associated numerous times (in individual studies as well
as several meta-analyses) with this type of cancer, yet it was also shown that fibrosis and viral
infection can lead to an up-regulation of GP73 in liver tissue. Therefore, it is debatable whether
this potential biomarker by itself is clinically useful or not. The authors should include this
discussion point in the text. The methodology is not novel as it uses the well described and robust
Cochrane approach for meta-analyses. Several issues however need to be addressed:
1) the abstract mentions that data sources such as PubMed were searched up to March 2023, yet
in the Search strategy section, it is written that "The search was updated to November 30, 2021."
Firstly, what was it updated from? This is confusing and needs to be explained. Secondly, was
the search conducted with a cut-off date in 2021 or 2023? Such inconsistencies, especially in
a meta-analysis, are not tolerable.
2) P-values appear to have been rounded or stated as "P > 0.05" for example. Rounding these
values or just stating if they are above or below a cut-off point is ok IF the exact values are stated
somewhere in the manuscript. Unfortunately, this is not the case and needs to be corrected.
3) Typos and confusing sentences: It would be beneficial for the reader if the authors can use
the help of a native English speaker to restructure sentences and paragraphs in certain parts
to make the text more understandable. Examples are: "perfoemed" to "performed", "patients
were not hepatocellular carcinoma" to "patients who did not have hepatocellular carcinoma",
"The p < 0.05 was considered" to "A p-value of less than 0.05 was considered", "The detail
processes of study selection were showed in" to "The detailed processes of study selection
are shown in", "the enrolled studies were shown in Table 1" to "the enrolled studies are
shown in Table 1", the paragraph titled "tGP73 and OS in HCC" needs to be re-written as it's
confusing and badly written, changes in the Discussion section: "almost no expression in normal
hepatocytes. Previous studies have proved" to "almost no expression in normal hepatocytes has
been observed. Previous studies have shown", "may be the sources of high heterogeneity." to
"may be the source of high heterogeneity.", "remains to be further studied" to "remains to be
studied further", "follow-up time have been proved" to "follow-up time have been proven",
"our meta-analysis showed" to "our meta-analysis shows", "our results showed" to "our results
indicate", "a larger sample of prospective studies are needed" to "a larger sample of prospective
studies is needed". Also, please remove the Acknowledgements section, authors do not need to
thank each other for their contributions.
Title: A meta-analysis of the prognostic impact of tissue Golgi protein 73(tGP73) in
hepatocellular carcinoma
Version: 1 Date: 15 Oct 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This manuscript describes a meta-analysis of studies investigating
the beneficial use of liver tissue-expressed GP73 as a prognostic marker for liver cancer. My
overall impression is that this study is mainly confirmatory of other recently published meta-
analyses involving liver disease and serum GP73 (2 alone this year), however, as far as I
know, no meta-analysis focussing on tissue-expressed GP73 has been published so far. The
methodology used by the authors is based on the Cochrane Review manager and data analysis
software. The authors identified 12 datasets from 10 studies. All expected parameters are well
described and fully disclosed, including the PRISM chart, appropriate dataset description, and
outputs. The study does meet best practice. While the study cohort is quite small for this type of
analysis, the methodology is valid and applied appropriately. The only criticism I have is that
there are some discrepancies in the text that need addressing, as well as English language editing.
This study has its merits, though solely on the grounds that a meta-analysis of tissue expressed
GP73 associated with hepatocellular carcinoma has not been published so far. However, one
could argue that serum GP73 has been associated numerous times (in individual studies as well
as several meta-analyses) with this type of cancer, yet it was also shown that fibrosis and viral
infection can lead to an up-regulation of GP73 in liver tissue. Therefore, it is debatable whether
this potential biomarker by itself is clinically useful or not. The authors should include this
discussion point in the text. The methodology is not novel as it uses the well described and robust
Cochrane approach for meta-analyses. Several issues however need to be addressed:
1) the abstract mentions that data sources such as PubMed were searched up to March 2023, yet
in the Search strategy section, it is written that "The search was updated to November 30, 2021."
Firstly, what was it updated from? This is confusing and needs to be explained. Secondly, was
the search conducted with a cut-off date in 2021 or 2023? Such inconsistencies, especially in
a meta-analysis, are not tolerable.
2) P-values appear to have been rounded or stated as "P > 0.05" for example. Rounding these
values or just stating if they are above or below a cut-off point is ok IF the exact values are stated
somewhere in the manuscript. Unfortunately, this is not the case and needs to be corrected.
3) Typos and confusing sentences: It would be beneficial for the reader if the authors can use
the help of a native English speaker to restructure sentences and paragraphs in certain parts
to make the text more understandable. Examples are: "perfoemed" to "performed", "patients
were not hepatocellular carcinoma" to "patients who did not have hepatocellular carcinoma",
"The p < 0.05 was considered" to "A p-value of less than 0.05 was considered", "The detail
processes of study selection were showed in" to "The detailed processes of study selection
are shown in", "the enrolled studies were shown in Table 1" to "the enrolled studies are
shown in Table 1", the paragraph titled "tGP73 and OS in HCC" needs to be re-written as it's
confusing and badly written, changes in the Discussion section: "almost no expression in normal
hepatocytes. Previous studies have proved" to "almost no expression in normal hepatocytes has
been observed. Previous studies have shown", "may be the sources of high heterogeneity." to
"may be the source of high heterogeneity.", "remains to be further studied" to "remains to be
studied further", "follow-up time have been proved" to "follow-up time have been proven",
"our meta-analysis showed" to "our meta-analysis shows", "our results showed" to "our results
indicate", "a larger sample of prospective studies are needed" to "a larger sample of prospective
studies is needed". Also, please remove the Acknowledgements section, authors do not need to
thank each other for their contributions.
Please review this paper.
user
Title: A meta-analysis of the prognostic impact of tissue Golgi protein 73(tGP73) in
hepatocellular carcinoma
Version: 1 Date: 15 Oct 2023
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
Yes - experiments and analyses were performed appropriately
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
Yes - the author's interpretation is reasonable
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This manuscript describes a meta-analysis of studies investigating
the beneficial use of liver tissue-expressed GP73 as a prognostic marker for liver cancer. My
overall impression is that this study is mainly confirmatory of other recently published meta-
analyses involving liver disease and serum GP73 (2 alone this year), however, as far as I
know, no meta-analysis focussing on tissue-expressed GP73 has been published so far. The
methodology used by the authors is based on the Cochrane Review manager and data analysis
software. The authors identified 12 datasets from 10 studies. All expected parameters are well
described and fully disclosed, including the PRISM chart, appropriate dataset description, and
outputs. The study does meet best practice. While the study cohort is quite small for this type of
analysis, the methodology is valid and applied appropriately. The only criticism I have is that
there are some discrepancies in the text that need addressing, as well as English language editing.
This study has its merits, though solely on the grounds that a meta-analysis of tissue expressed
GP73 associated with hepatocellular carcinoma has not been published so far. However, one
could argue that serum GP73 has been associated numerous times (in individual studies as well
as several meta-analyses) with this type of cancer, yet it was also shown that fibrosis and viral
infection can lead to an up-regulation of GP73 in liver tissue. Therefore, it is debatable whether
this potential biomarker by itself is clinically useful or not. The authors should include this
discussion point in the text. The methodology is not novel as it uses the well described and robust
Cochrane approach for meta-analyses. Several issues however need to be addressed:
1) the abstract mentions that data sources such as PubMed were searched up to March 2023, yet
in the Search strategy section, it is written that "The search was updated to November 30, 2021."
Firstly, what was it updated from? This is confusing and needs to be explained. Secondly, was
the search conducted with a cut-off date in 2021 or 2023? Such inconsistencies, especially in
a meta-analysis, are not tolerable.
2) P-values appear to have been rounded or stated as "P > 0.05" for example. Rounding these
values or just stating if they are above or below a cut-off point is ok IF the exact values are stated
somewhere in the manuscript. Unfortunately, this is not the case and needs to be corrected.
3) Typos and confusing sentences: It would be beneficial for the reader if the authors can use
the help of a native English speaker to restructure sentences and paragraphs in certain parts
to make the text more understandable. Examples are: "perfoemed" to "performed", "patients
were not hepatocellular carcinoma" to "patients who did not have hepatocellular carcinoma",
"The p < 0.05 was considered" to "A p-value of less than 0.05 was considered", "The detail
processes of study selection were showed in" to "The detailed processes of study selection
are shown in", "the enrolled studies were shown in Table 1" to "the enrolled studies are
shown in Table 1", the paragraph titled "tGP73 and OS in HCC" needs to be re-written as it's
confusing and badly written, changes in the Discussion section: "almost no expression in normal
hepatocytes. Previous studies have proved" to "almost no expression in normal hepatocytes has
been observed. Previous studies have shown", "may be the sources of high heterogeneity." to
"may be the source of high heterogeneity.", "remains to be further studied" to "remains to be
studied further", "follow-up time have been proved" to "follow-up time have been proven",
"our meta-analysis showed" to "our meta-analysis shows", "our results showed" to "our results
indicate", "a larger sample of prospective studies are needed" to "a larger sample of prospective
studies is needed". Also, please remove the Acknowledgements section, authors do not need to
thank each other for their contributions.
assistant