Review for 10.1186/s12876-023-02672-z (2023)

Title: A comprehensive computational analysis to explore the importance of SIGLECs in HCC
biology
Version: 5 Date: 09 Aug 2022
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)?
No - there are major issues
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
No - manuscript has some fundamental flaw(s)
PEER REVIEWER COMMENTS:
GENERAL COMMENTS:
Must admit I found the computational analytical pipeline confusing and also was not convinced
by how their conclusion was made regarding SIGLEC as a predictive biomarker for sorafenib
response.
REQUESTED REVISIONS:
Based on what the authors have presented/concluded losing SIGLECs expression is a poor
prognostic marker and potentially useful to use as a predictive biomarker of response to sorafenib
but this computational work definitely needs more clarification and validation. The following
are my comments.
Major Comments
Authors need to summarise what literature there is on HCC and SIGLECs (intro/discussion)
In methods, you need to also state if any cirrhotic background liver was included
In data extraction and analysis section of methods, this very confusing to read. A flow chart of
your analytical pipeline will be of use. You also need to state when you accessed programmes
for analysis and which versions used. You only used a data visualization package from R, you
can’t say you programmed R to do your analysis for you.
Datasets downloaded ICGC-LIRI-JP+ GSE22058 + GSE14520 can you include disease
aetiology ie was it all HBV. If yes, you need to clearly state in abstract too.
Can you add TNM or BCLC staging for HCC.
To confirm did you restrict analysis to advanced HCC only, when looking at sorafenib response,
if yes, define advanced HCC in methods.
Also I am unclear on what systemic therapy patients went on in the downloaded datasets so I
am not sure how the authors are able to make the conclusions that they do about SIGLEC use as
a predictive biomarker eg for sorafenib. Later on the authors then say they filtered for sorafenib
cases, what did they compare to eg all other HCC cases or equivalent HCC stage but did not
receive systemic therapy. And what are the number of sorafenib cases etc?
What is your normal liver ? non cirrhotic only, you need cirrhotic controls too.
Minor Comments:
Sorafenib has now been overtaken by immunotherapy as first line option in advanced HCC now,
so would rephrase your statement in the abstract
Conclusion of abstract a bit strong change “considerable” to potential
In introduction, authors say radical surgery maybe rephrase to resection & liver transplant.
Poor prognosis in HCC is a combination of late diagnosis as stated by the authors and the fact that
the majority of cases develop on the background of cirrhosis. At some point in the introduction
the authors need to mention cirrhosis.
Not sure on journal style but I am not used to the conclusion being at the end of the intro. At
end of intro would just state you are doing a computational analysis to explore the importance
SIGLECs in HCC biology/prognosis
When using abbreviations for the first time please define in the main text too."