Title: A comprehensive computational analysis to explore the importance of SIGLECs in HCC
biology
Version: 1 Date: 24 Nov 2021
Reviewer's report:
General comment
HCC represents one of the most frequent cancer-related death worldwide and, despite the
advances in HCC management, prognosis is still poor due to the diagnosis at advanced stage.
Sorafenib has dominated the field of systemic therapy for HCC for more than a decade  but,
since its approval, no markers predicting of response has bee identified. The paper by Yao et
al. evaluate the role of a family of sialic acid-recognition protein (Siglec) into predicting the
response to therapy. Despite this, there are several lines of information which are missing and
preclude to appropriately evaluate the manuscript.
Major issues
1) A role for siglec in predicting overall survival has been described for HBV-related HCC.
Additional clinical information about aetiology of liver disease, presence of cirrhosis, alpha-
fetoprotein values, tumor burden etc should be added in the text to confirm the role of Siglec
for HCC patients who are started of sorafenib.
2) Authors describe results of overall survival, RFS and PFS. First of all, a definition for all these
endpoint should be added in the statistical analysis paragraph. Moreover, if patients are started
on sorafenib they are not free from CC and recurrence free survival is not a good endpoint to
be evaluated.
3) Which role could SIglec play in predicting the response to new first lines of therapy
(atezolizumab+bevacizumab)?
Minor issues
1) All abbreviations used in the text should be explained as in table and figure legends
Title: A comprehensive computational analysis to explore the importance of SIGLECs in HCC
biology
Version: 1 Date: 24 Nov 2021
Reviewer's report:
General comment
HCC represents one of the most frequent cancer-related death worldwide and, despite the
advances in HCC management, prognosis is still poor due to the diagnosis at advanced stage.
Sorafenib has dominated the field of systemic therapy for HCC for more than a decade  but,
since its approval, no markers predicting of response has bee identified. The paper by Yao et
al. evaluate the role of a family of sialic acid-recognition protein (Siglec) into predicting the
response to therapy. Despite this, there are several lines of information which are missing and
preclude to appropriately evaluate the manuscript.
Major issues
1) A role for siglec in predicting overall survival has been described for HBV-related HCC.
Additional clinical information about aetiology of liver disease, presence of cirrhosis, alpha-
fetoprotein values, tumor burden etc should be added in the text to confirm the role of Siglec
for HCC patients who are started of sorafenib.
2) Authors describe results of overall survival, RFS and PFS. First of all, a definition for all these
endpoint should be added in the statistical analysis paragraph. Moreover, if patients are started
on sorafenib they are not free from CC and recurrence free survival is not a good endpoint to
be evaluated.
3) Which role could SIglec play in predicting the response to new first lines of therapy
(atezolizumab+bevacizumab)?
Minor issues
1) All abbreviations used in the text should be explained as in table and figure legends
Please review this paper.
user
Title: A comprehensive computational analysis to explore the importance of SIGLECs in HCC
biology
Version: 1 Date: 24 Nov 2021
Reviewer's report:
General comment
HCC represents one of the most frequent cancer-related death worldwide and, despite the
advances in HCC management, prognosis is still poor due to the diagnosis at advanced stage.
Sorafenib has dominated the field of systemic therapy for HCC for more than a decade  but,
since its approval, no markers predicting of response has bee identified. The paper by Yao et
al. evaluate the role of a family of sialic acid-recognition protein (Siglec) into predicting the
response to therapy. Despite this, there are several lines of information which are missing and
preclude to appropriately evaluate the manuscript.
Major issues
1) A role for siglec in predicting overall survival has been described for HBV-related HCC.
Additional clinical information about aetiology of liver disease, presence of cirrhosis, alpha-
fetoprotein values, tumor burden etc should be added in the text to confirm the role of Siglec
for HCC patients who are started of sorafenib.
2) Authors describe results of overall survival, RFS and PFS. First of all, a definition for all these
endpoint should be added in the statistical analysis paragraph. Moreover, if patients are started
on sorafenib they are not free from CC and recurrence free survival is not a good endpoint to
be evaluated.
3) Which role could SIglec play in predicting the response to new first lines of therapy
(atezolizumab+bevacizumab)?
Minor issues
1) All abbreviations used in the text should be explained as in table and figure legends
assistant