Title: Effect and potential mechanism of oncometabolite succinate promotes distant metastasis
of colorectal cancer by activating STAT3
Version: 2 Date: 23 Oct 2023
Reviewer's report:
This manuscript describes that succinate can increase p-STAT3 expression, promote the EMT
process, and promote the distant metastasis of colorectal cancer. This report is a bit lacking in
novelty. There are several points in this manuscript that need to be improved, which are listed
below.
1. This report is a bit lacking in novelty. For example, Previous studies have already shown that
succinate activates EMT via the HIF1a-PI3k axis and promotes distant metastasis. However, you
should accurately describe and discuss previous studies on the relationship between succinate
and distant metastasis in the background or discussion section.
2. Could you show the impact of increased succinate content on patient prognosis (overall
survival, DFS, etc.) with the data from your institution and add it to Figure 1? Data relating
succinate content to distant metastasis would be desirable.
3. The reason for focusing on the relationship between succinic acid and STAT3 and EMT
is unclear. Could you indicate the results of any gene expression analysis (e.g. RNA-seq)
or pathway analysis? It has been previously reported that succinic acid promotes STAT3
phosphorylation and that succinic acid activates EMT.
4. In all the figures in Fig. 3, could you add and compare the results of succinate alone added
to SW480 and HCT and the negative control results.
5. In Figure 4, please add the experimental system in which HO-3867 is administered to mice.
This manuscript needs as much novelty as possible in order to be accepted.
6. The description in section 4.10 Statistical Analysis is not accurate. The statistical analyses
used should not be only one-way ANOVA or Kruskal-Wallis test. Moreover, it should be clear
which statistical test was used to generate every P-value. These data should be analyzed using
tests that are adequate for multiple groups, such as analysis of variance (ANOVA) followed by
a post hoc test (e.g. Tukey, Bonferroni, Dunnett, etc.) for parametric data, or Kruskal-Wallis test
followed by Dunn's test for non-parametric data.
Title: Effect and potential mechanism of oncometabolite succinate promotes distant metastasis
of colorectal cancer by activating STAT3
Version: 2 Date: 23 Oct 2023
Reviewer's report:
This manuscript describes that succinate can increase p-STAT3 expression, promote the EMT
process, and promote the distant metastasis of colorectal cancer. This report is a bit lacking in
novelty. There are several points in this manuscript that need to be improved, which are listed
below.
1. This report is a bit lacking in novelty. For example, Previous studies have already shown that
succinate activates EMT via the HIF1a-PI3k axis and promotes distant metastasis. However, you
should accurately describe and discuss previous studies on the relationship between succinate
and distant metastasis in the background or discussion section.
2. Could you show the impact of increased succinate content on patient prognosis (overall
survival, DFS, etc.) with the data from your institution and add it to Figure 1? Data relating
succinate content to distant metastasis would be desirable.
3. The reason for focusing on the relationship between succinic acid and STAT3 and EMT
is unclear. Could you indicate the results of any gene expression analysis (e.g. RNA-seq)
or pathway analysis? It has been previously reported that succinic acid promotes STAT3
phosphorylation and that succinic acid activates EMT.
4. In all the figures in Fig. 3, could you add and compare the results of succinate alone added
to SW480 and HCT and the negative control results.
5. In Figure 4, please add the experimental system in which HO-3867 is administered to mice.
This manuscript needs as much novelty as possible in order to be accepted.
6. The description in section 4.10 Statistical Analysis is not accurate. The statistical analyses
used should not be only one-way ANOVA or Kruskal-Wallis test. Moreover, it should be clear
which statistical test was used to generate every P-value. These data should be analyzed using
tests that are adequate for multiple groups, such as analysis of variance (ANOVA) followed by
a post hoc test (e.g. Tukey, Bonferroni, Dunnett, etc.) for parametric data, or Kruskal-Wallis test
followed by Dunn's test for non-parametric data.
Please review this paper.
user
Title: Effect and potential mechanism of oncometabolite succinate promotes distant metastasis
of colorectal cancer by activating STAT3
Version: 2 Date: 23 Oct 2023
Reviewer's report:
This manuscript describes that succinate can increase p-STAT3 expression, promote the EMT
process, and promote the distant metastasis of colorectal cancer. This report is a bit lacking in
novelty. There are several points in this manuscript that need to be improved, which are listed
below.
1. This report is a bit lacking in novelty. For example, Previous studies have already shown that
succinate activates EMT via the HIF1a-PI3k axis and promotes distant metastasis. However, you
should accurately describe and discuss previous studies on the relationship between succinate
and distant metastasis in the background or discussion section.
2. Could you show the impact of increased succinate content on patient prognosis (overall
survival, DFS, etc.) with the data from your institution and add it to Figure 1? Data relating
succinate content to distant metastasis would be desirable.
3. The reason for focusing on the relationship between succinic acid and STAT3 and EMT
is unclear. Could you indicate the results of any gene expression analysis (e.g. RNA-seq)
or pathway analysis? It has been previously reported that succinic acid promotes STAT3
phosphorylation and that succinic acid activates EMT.
4. In all the figures in Fig. 3, could you add and compare the results of succinate alone added
to SW480 and HCT and the negative control results.
5. In Figure 4, please add the experimental system in which HO-3867 is administered to mice.
This manuscript needs as much novelty as possible in order to be accepted.
6. The description in section 4.10 Statistical Analysis is not accurate. The statistical analyses
used should not be only one-way ANOVA or Kruskal-Wallis test. Moreover, it should be clear
which statistical test was used to generate every P-value. These data should be analyzed using
tests that are adequate for multiple groups, such as analysis of variance (ANOVA) followed by
a post hoc test (e.g. Tukey, Bonferroni, Dunnett, etc.) for parametric data, or Kruskal-Wallis test
followed by Dunn's test for non-parametric data.
assistant