Title: Comprehensive analysis of candidate signatures of long non-coding RNA LINC01116
and related protein-coding genes in patients with hepatocellular carcinoma
Version: 2 Date: 27 Feb 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)?
No - there are minor issues
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?
No - there are minor issues
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?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This study sought to investigate expression of LINC01116 and
correlated protein coding genes in HCC tumor versus non-tumor tissue. Overall, the study
seems exploratory, providing results that suggest correlations, prognostic/diagnostic potential,
and putative drug targets, but without any in vitro or in vivo experiments to confirm these
observations. The authors have looked at different aspects of LINC01116 involvement,
including generation of risk scores and methylation changes, which represents a broad
characterization approach.  The work would be significantly strengthened by validation of
findings using in vitro and in vivo characterization. In addition, it appears that the authors
explored LINC01116 within the context of HCC because of the lincRNA's involvement in other
kinds of cancers. This is not a very strong reason to pursue the study of a lincRNA. Is there
a biological rationale for thinking that LINC01116 might be important in the development of
HCC?
REQUESTED REVISIONS:
1. Since this manuscript was submitted for review, a paper has been published (Tao et al,
2022) that examined LINC01116 expression in the TCGA dataset. The main findings were that
LINC01116 is an immune-related oncogene that is associated with EMT and immune-regulation
in HCC. In vitro and in vivo experiments demonstrated that LINC01116 stimulated cell
proliferation, cell cycle progression, and tumor metastasis. This study complements the current
study well and the authors are encouraged to implement these findings into the Discussion
section to provide a deeper understanding of LINC01116 in HCC.
2. GSEA was performed to explore potential molecular mechanisms and a FDR
Title: Comprehensive analysis of candidate signatures of long non-coding RNA LINC01116
and related protein-coding genes in patients with hepatocellular carcinoma
Version: 2 Date: 27 Feb 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)?
No - there are minor issues
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?
No - there are minor issues
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?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This study sought to investigate expression of LINC01116 and
correlated protein coding genes in HCC tumor versus non-tumor tissue. Overall, the study
seems exploratory, providing results that suggest correlations, prognostic/diagnostic potential,
and putative drug targets, but without any in vitro or in vivo experiments to confirm these
observations. The authors have looked at different aspects of LINC01116 involvement,
including generation of risk scores and methylation changes, which represents a broad
characterization approach.  The work would be significantly strengthened by validation of
findings using in vitro and in vivo characterization. In addition, it appears that the authors
explored LINC01116 within the context of HCC because of the lincRNA's involvement in other
kinds of cancers. This is not a very strong reason to pursue the study of a lincRNA. Is there
a biological rationale for thinking that LINC01116 might be important in the development of
HCC?
REQUESTED REVISIONS:
1. Since this manuscript was submitted for review, a paper has been published (Tao et al,
2022) that examined LINC01116 expression in the TCGA dataset. The main findings were that
LINC01116 is an immune-related oncogene that is associated with EMT and immune-regulation
in HCC. In vitro and in vivo experiments demonstrated that LINC01116 stimulated cell
proliferation, cell cycle progression, and tumor metastasis. This study complements the current
study well and the authors are encouraged to implement these findings into the Discussion
section to provide a deeper understanding of LINC01116 in HCC.
2. GSEA was performed to explore potential molecular mechanisms and a FDR
Please review this paper.
user
Title: Comprehensive analysis of candidate signatures of long non-coding RNA LINC01116
and related protein-coding genes in patients with hepatocellular carcinoma
Version: 2 Date: 27 Feb 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)?
No - there are minor issues
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?
No - there are minor issues
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?
Maybe - with major revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: This study sought to investigate expression of LINC01116 and
correlated protein coding genes in HCC tumor versus non-tumor tissue. Overall, the study
seems exploratory, providing results that suggest correlations, prognostic/diagnostic potential,
and putative drug targets, but without any in vitro or in vivo experiments to confirm these
observations. The authors have looked at different aspects of LINC01116 involvement,
including generation of risk scores and methylation changes, which represents a broad
characterization approach.  The work would be significantly strengthened by validation of
findings using in vitro and in vivo characterization. In addition, it appears that the authors
explored LINC01116 within the context of HCC because of the lincRNA's involvement in other
kinds of cancers. This is not a very strong reason to pursue the study of a lincRNA. Is there
a biological rationale for thinking that LINC01116 might be important in the development of
HCC?
REQUESTED REVISIONS:
1. Since this manuscript was submitted for review, a paper has been published (Tao et al,
2022) that examined LINC01116 expression in the TCGA dataset. The main findings were that
LINC01116 is an immune-related oncogene that is associated with EMT and immune-regulation
in HCC. In vitro and in vivo experiments demonstrated that LINC01116 stimulated cell
proliferation, cell cycle progression, and tumor metastasis. This study complements the current
study well and the authors are encouraged to implement these findings into the Discussion
section to provide a deeper understanding of LINC01116 in HCC.
2. GSEA was performed to explore potential molecular mechanisms and a FDR
assistant