Title: Construction of immune-related lncRNA signature to predict aggressiveness, immune
landscape, and drug resistance of colon cancer
Version: 2 Date: 23 Oct 2021
Reviewer's report:
In the manuscript#the authors took advantage of the transcriptome data of the TCGA-COAD
cohort to construct two immune-related lncRNA-based models which predict the clinical
outcomes of colorectal cancer patients. Then the authors further compared the immune cell
infiltration, the expression of TGFB1 and LAG3, predicted drug susceptibility between high-
risk and low-risk groups. Functional GSEA analyses were also performed. The overall design
of this study is sound. However, there are questions/comments for the authors as follows:
1)The language in the manuscript should be further polished by a native English speaker.
2)The LASSO regression model. The description of this model is not sufficiently detailed. Why
was this model chosen? As far as I know, the result of each run for the model is quite different.
So what are the criteria for final model determination?#AIC, BIC or other criteria). These have
to be explained in detail.
3)The authors developed two risk models in this study: the pair-risk model and the exp-risk
model. No comparison of these two models was conducted. The GSEA analysis was only
performed based on the exp-risk model. Therefore, readers may get confused about the purpose
and the point of establishing two models.
4)No FDR or multiple hypothesis testing was done. In other words, P values were not adjusted,
such as Fig.2A-2B#Fig 3C#Fig. 4E-G, et al.
5)As the author only utilized that the data of the TCGA-COAD cohort instead of the combination
of TCGA-COAD and TCGA-READ, the 'colorectal cancer' is not an accurate description. There
seems to be no R package called 'survivor.' The primary endpoint of this study#DFS or OS) was
missing in the manuscript.
6)Suggestions for figures and supplementary materials. To make the results more readable, it is
recommended that Figure 2A-B only displays the result for 11 core immune lncRNAs. Results of
the rest meaningful irlncRNAs can be added to the supplementary materials. Besides, the authors
calculated the infiltration of the immune cells with seven acknowledged algorithms, which
deserves recognition. However, overlapped and consistent results should be emphasized, as this
could give us more confidence in the authors' conclusions. Meanwhile, consider integrating
the consistent results into one single graph for readability instead of multiple boxplots. Please
consider other types of plots for presentation.
7)Apart from LAG3, multiple classical immune checkpoints should be included in the analysis,
such as PD-1/PD-L1, CTLA4, TIM3#TIGIT, et al. In figure 7C-G#the IC50 of several drugs
were compared between two risk groups. A detailed description of these drugs should be
included in the main text.
8)The risk models proposed by the authors were not validated in an independent cohort.
9)The discussion section should emphasize the role of selected 11 lncRNAs in cancers and their
immune correlation in cancers.
Title: Construction of immune-related lncRNA signature to predict aggressiveness, immune
landscape, and drug resistance of colon cancer
Version: 2 Date: 23 Oct 2021
Reviewer's report:
In the manuscript#the authors took advantage of the transcriptome data of the TCGA-COAD
cohort to construct two immune-related lncRNA-based models which predict the clinical
outcomes of colorectal cancer patients. Then the authors further compared the immune cell
infiltration, the expression of TGFB1 and LAG3, predicted drug susceptibility between high-
risk and low-risk groups. Functional GSEA analyses were also performed. The overall design
of this study is sound. However, there are questions/comments for the authors as follows:
1)The language in the manuscript should be further polished by a native English speaker.
2)The LASSO regression model. The description of this model is not sufficiently detailed. Why
was this model chosen? As far as I know, the result of each run for the model is quite different.
So what are the criteria for final model determination?#AIC, BIC or other criteria). These have
to be explained in detail.
3)The authors developed two risk models in this study: the pair-risk model and the exp-risk
model. No comparison of these two models was conducted. The GSEA analysis was only
performed based on the exp-risk model. Therefore, readers may get confused about the purpose
and the point of establishing two models.
4)No FDR or multiple hypothesis testing was done. In other words, P values were not adjusted,
such as Fig.2A-2B#Fig 3C#Fig. 4E-G, et al.
5)As the author only utilized that the data of the TCGA-COAD cohort instead of the combination
of TCGA-COAD and TCGA-READ, the 'colorectal cancer' is not an accurate description. There
seems to be no R package called 'survivor.' The primary endpoint of this study#DFS or OS) was
missing in the manuscript.
6)Suggestions for figures and supplementary materials. To make the results more readable, it is
recommended that Figure 2A-B only displays the result for 11 core immune lncRNAs. Results of
the rest meaningful irlncRNAs can be added to the supplementary materials. Besides, the authors
calculated the infiltration of the immune cells with seven acknowledged algorithms, which
deserves recognition. However, overlapped and consistent results should be emphasized, as this
could give us more confidence in the authors' conclusions. Meanwhile, consider integrating
the consistent results into one single graph for readability instead of multiple boxplots. Please
consider other types of plots for presentation.
7)Apart from LAG3, multiple classical immune checkpoints should be included in the analysis,
such as PD-1/PD-L1, CTLA4, TIM3#TIGIT, et al. In figure 7C-G#the IC50 of several drugs
were compared between two risk groups. A detailed description of these drugs should be
included in the main text.
8)The risk models proposed by the authors were not validated in an independent cohort.
9)The discussion section should emphasize the role of selected 11 lncRNAs in cancers and their
immune correlation in cancers.
Please review this paper.
user
Title: Construction of immune-related lncRNA signature to predict aggressiveness, immune
landscape, and drug resistance of colon cancer
Version: 2 Date: 23 Oct 2021
Reviewer's report:
In the manuscript#the authors took advantage of the transcriptome data of the TCGA-COAD
cohort to construct two immune-related lncRNA-based models which predict the clinical
outcomes of colorectal cancer patients. Then the authors further compared the immune cell
infiltration, the expression of TGFB1 and LAG3, predicted drug susceptibility between high-
risk and low-risk groups. Functional GSEA analyses were also performed. The overall design
of this study is sound. However, there are questions/comments for the authors as follows:
1)The language in the manuscript should be further polished by a native English speaker.
2)The LASSO regression model. The description of this model is not sufficiently detailed. Why
was this model chosen? As far as I know, the result of each run for the model is quite different.
So what are the criteria for final model determination?#AIC, BIC or other criteria). These have
to be explained in detail.
3)The authors developed two risk models in this study: the pair-risk model and the exp-risk
model. No comparison of these two models was conducted. The GSEA analysis was only
performed based on the exp-risk model. Therefore, readers may get confused about the purpose
and the point of establishing two models.
4)No FDR or multiple hypothesis testing was done. In other words, P values were not adjusted,
such as Fig.2A-2B#Fig 3C#Fig. 4E-G, et al.
5)As the author only utilized that the data of the TCGA-COAD cohort instead of the combination
of TCGA-COAD and TCGA-READ, the 'colorectal cancer' is not an accurate description. There
seems to be no R package called 'survivor.' The primary endpoint of this study#DFS or OS) was
missing in the manuscript.
6)Suggestions for figures and supplementary materials. To make the results more readable, it is
recommended that Figure 2A-B only displays the result for 11 core immune lncRNAs. Results of
the rest meaningful irlncRNAs can be added to the supplementary materials. Besides, the authors
calculated the infiltration of the immune cells with seven acknowledged algorithms, which
deserves recognition. However, overlapped and consistent results should be emphasized, as this
could give us more confidence in the authors' conclusions. Meanwhile, consider integrating
the consistent results into one single graph for readability instead of multiple boxplots. Please
consider other types of plots for presentation.
7)Apart from LAG3, multiple classical immune checkpoints should be included in the analysis,
such as PD-1/PD-L1, CTLA4, TIM3#TIGIT, et al. In figure 7C-G#the IC50 of several drugs
were compared between two risk groups. A detailed description of these drugs should be
included in the main text.
8)The risk models proposed by the authors were not validated in an independent cohort.
9)The discussion section should emphasize the role of selected 11 lncRNAs in cancers and their
immune correlation in cancers.
assistant