Title: Construction of a prognostic risk model based on apoptosis-related genes to assess tumor
immune microenvironment and predict prognosis in hepatocellular carcinoma
Version: 1 Date: 10 Jul 2022
Reviewer:  Yutaka Midorikawa
Reviewer's report:
Comment on the manuscript a5bc75ba-fdc4-4ca5-b984-7c52c11a7f0e by Wang, et al.
Despite of curative resection, HCC often relapse because of high grade of malignancy. This
paper established the risk score using 9 apoptosis-related genes from the TCGA data, which
could predict the patient survivals. The concept of the paper in intriguing, however, there are
major concerns that need to be addressed.
There are several questions and suggestions for corrections:
1) Study design is confusing. Nine apoptosis-related genes with expression aberration between
cluster A and B were selected. Using these predictor genes, the authors constructed risk score
and divided HCC patients into the high and low risk groups based on survival data. However,
I assume that it is a matter of course because these predictor genes were selected and validated
from the same TCGA cohort; 9 ARGs in high risk group were selected from Cluster A and those
in low risk group from Cluster B. Survival curves in Figure 3E should have been validated using
the independent cohort such as ICGC.
2) Similarly, nomogram in Figure 6A should have been validated using another cohort, not
TCGA.
3) It is not clear that only the apoptosis-related genes were focused for construction of risk score.
How about the expression of genes in the other categories?
4) Discussion about Figure 4F is insufficient.
5) The last sentence of Introduction should be removed because it is one of conclusions.
6) The word “gene signature” in the title or Figure 3 is inadequate because there is no data about
gene signature in this report.
Title: Construction of a prognostic risk model based on apoptosis-related genes to assess tumor
immune microenvironment and predict prognosis in hepatocellular carcinoma
Version: 1 Date: 10 Jul 2022
Reviewer:  Yutaka Midorikawa
Reviewer's report:
Comment on the manuscript a5bc75ba-fdc4-4ca5-b984-7c52c11a7f0e by Wang, et al.
Despite of curative resection, HCC often relapse because of high grade of malignancy. This
paper established the risk score using 9 apoptosis-related genes from the TCGA data, which
could predict the patient survivals. The concept of the paper in intriguing, however, there are
major concerns that need to be addressed.
There are several questions and suggestions for corrections:
1) Study design is confusing. Nine apoptosis-related genes with expression aberration between
cluster A and B were selected. Using these predictor genes, the authors constructed risk score
and divided HCC patients into the high and low risk groups based on survival data. However,
I assume that it is a matter of course because these predictor genes were selected and validated
from the same TCGA cohort; 9 ARGs in high risk group were selected from Cluster A and those
in low risk group from Cluster B. Survival curves in Figure 3E should have been validated using
the independent cohort such as ICGC.
2) Similarly, nomogram in Figure 6A should have been validated using another cohort, not
TCGA.
3) It is not clear that only the apoptosis-related genes were focused for construction of risk score.
How about the expression of genes in the other categories?
4) Discussion about Figure 4F is insufficient.
5) The last sentence of Introduction should be removed because it is one of conclusions.
6) The word “gene signature” in the title or Figure 3 is inadequate because there is no data about
gene signature in this report.
Please review this paper.
user
Title: Construction of a prognostic risk model based on apoptosis-related genes to assess tumor
immune microenvironment and predict prognosis in hepatocellular carcinoma
Version: 1 Date: 10 Jul 2022
Reviewer:  Yutaka Midorikawa
Reviewer's report:
Comment on the manuscript a5bc75ba-fdc4-4ca5-b984-7c52c11a7f0e by Wang, et al.
Despite of curative resection, HCC often relapse because of high grade of malignancy. This
paper established the risk score using 9 apoptosis-related genes from the TCGA data, which
could predict the patient survivals. The concept of the paper in intriguing, however, there are
major concerns that need to be addressed.
There are several questions and suggestions for corrections:
1) Study design is confusing. Nine apoptosis-related genes with expression aberration between
cluster A and B were selected. Using these predictor genes, the authors constructed risk score
and divided HCC patients into the high and low risk groups based on survival data. However,
I assume that it is a matter of course because these predictor genes were selected and validated
from the same TCGA cohort; 9 ARGs in high risk group were selected from Cluster A and those
in low risk group from Cluster B. Survival curves in Figure 3E should have been validated using
the independent cohort such as ICGC.
2) Similarly, nomogram in Figure 6A should have been validated using another cohort, not
TCGA.
3) It is not clear that only the apoptosis-related genes were focused for construction of risk score.
How about the expression of genes in the other categories?
4) Discussion about Figure 4F is insufficient.
5) The last sentence of Introduction should be removed because it is one of conclusions.
6) The word “gene signature” in the title or Figure 3 is inadequate because there is no data about
gene signature in this report.
assistant