Title: Establishment of a prognostic signature based on fatty acid metabolism genes in HCC
associated with hepatitis B
Version: 2 Date: 19 Mar 2023
Reviewer's report:
The authors' findings suggest a strong connection between fatty acid metabolism (FAM) and
HBV-associated HCC. Through LASSO-penalized Cox regression, the authors constructed a
prognostic model using data from the TCGA database. The model was then validated by their
in-house cohort of HBV-associated HCC patients. Further studies indicated that targeting FAM
could be a strategy to block the accumulation of Tregs in the tumor microenvironment of HBV-
associated HCC. However, there are several concerns regarding their investigation.
Point 1: None of the subtitles in the RESULTS section are conclusive.
Point 2: In lines 193-195 of the manuscript, it is stated that “As a result, FAM pathway was
clearly enriched in adjacent normal tissue both in GSE94660 (Fig. 2A) and GSE121248 (Fig.
2C), indicating that most FAM genes are down-regulated in tumor tissue.”. It seems like the
results of the Fig. 2B, Fig. 2D, but not the Fig. 2A and Fig. 2C.
Point 3: Is there any relationship between the 12 genes in the Survival analysis section and the
5 genes in the Construction of the prognostic signature section? Besides, the descriptions about
these two parts are unclear.
Point 4: The author should provide a detailed description of the performance of the prognostic
signature in the GEO datasets (GSE94660 and GSE121248).
Point 5: What are the advantages of the prognostic signature in this study compared to other
previously reported predictive signatures? Better performance?
Point 6: Line 256, “To identify HBV-associated genes, mRNA expression level of the five-gene
signature was assessed between 30 HBV-positive and 15 HBV-negative HCC tumor tissue, and
in parental HepG2 cells compared with the daughter HepG2.2.15 cells containing two head-to-
tail dimers of HBV genomic DNA.”. The assessment of the mRNA expression levels of the five-
gene signature seems irrelevant to the identification of the HBV-associated genes.
Point 7: The author should give a reasonable explanation for the contradiction between the
Fig.8A and Fig.8B.
Title: Establishment of a prognostic signature based on fatty acid metabolism genes in HCC
associated with hepatitis B
Version: 2 Date: 19 Mar 2023
Reviewer's report:
The authors' findings suggest a strong connection between fatty acid metabolism (FAM) and
HBV-associated HCC. Through LASSO-penalized Cox regression, the authors constructed a
prognostic model using data from the TCGA database. The model was then validated by their
in-house cohort of HBV-associated HCC patients. Further studies indicated that targeting FAM
could be a strategy to block the accumulation of Tregs in the tumor microenvironment of HBV-
associated HCC. However, there are several concerns regarding their investigation.
Point 1: None of the subtitles in the RESULTS section are conclusive.
Point 2: In lines 193-195 of the manuscript, it is stated that “As a result, FAM pathway was
clearly enriched in adjacent normal tissue both in GSE94660 (Fig. 2A) and GSE121248 (Fig.
2C), indicating that most FAM genes are down-regulated in tumor tissue.”. It seems like the
results of the Fig. 2B, Fig. 2D, but not the Fig. 2A and Fig. 2C.
Point 3: Is there any relationship between the 12 genes in the Survival analysis section and the
5 genes in the Construction of the prognostic signature section? Besides, the descriptions about
these two parts are unclear.
Point 4: The author should provide a detailed description of the performance of the prognostic
signature in the GEO datasets (GSE94660 and GSE121248).
Point 5: What are the advantages of the prognostic signature in this study compared to other
previously reported predictive signatures? Better performance?
Point 6: Line 256, “To identify HBV-associated genes, mRNA expression level of the five-gene
signature was assessed between 30 HBV-positive and 15 HBV-negative HCC tumor tissue, and
in parental HepG2 cells compared with the daughter HepG2.2.15 cells containing two head-to-
tail dimers of HBV genomic DNA.”. The assessment of the mRNA expression levels of the five-
gene signature seems irrelevant to the identification of the HBV-associated genes.
Point 7: The author should give a reasonable explanation for the contradiction between the
Fig.8A and Fig.8B.
Please review this paper.
user
Title: Establishment of a prognostic signature based on fatty acid metabolism genes in HCC
associated with hepatitis B
Version: 2 Date: 19 Mar 2023
Reviewer's report:
The authors' findings suggest a strong connection between fatty acid metabolism (FAM) and
HBV-associated HCC. Through LASSO-penalized Cox regression, the authors constructed a
prognostic model using data from the TCGA database. The model was then validated by their
in-house cohort of HBV-associated HCC patients. Further studies indicated that targeting FAM
could be a strategy to block the accumulation of Tregs in the tumor microenvironment of HBV-
associated HCC. However, there are several concerns regarding their investigation.
Point 1: None of the subtitles in the RESULTS section are conclusive.
Point 2: In lines 193-195 of the manuscript, it is stated that “As a result, FAM pathway was
clearly enriched in adjacent normal tissue both in GSE94660 (Fig. 2A) and GSE121248 (Fig.
2C), indicating that most FAM genes are down-regulated in tumor tissue.”. It seems like the
results of the Fig. 2B, Fig. 2D, but not the Fig. 2A and Fig. 2C.
Point 3: Is there any relationship between the 12 genes in the Survival analysis section and the
5 genes in the Construction of the prognostic signature section? Besides, the descriptions about
these two parts are unclear.
Point 4: The author should provide a detailed description of the performance of the prognostic
signature in the GEO datasets (GSE94660 and GSE121248).
Point 5: What are the advantages of the prognostic signature in this study compared to other
previously reported predictive signatures? Better performance?
Point 6: Line 256, “To identify HBV-associated genes, mRNA expression level of the five-gene
signature was assessed between 30 HBV-positive and 15 HBV-negative HCC tumor tissue, and
in parental HepG2 cells compared with the daughter HepG2.2.15 cells containing two head-to-
tail dimers of HBV genomic DNA.”. The assessment of the mRNA expression levels of the five-
gene signature seems irrelevant to the identification of the HBV-associated genes.
Point 7: The author should give a reasonable explanation for the contradiction between the
Fig.8A and Fig.8B.
assistant