Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 4 Date: 24 Feb 2021
Reviewer's report:
The manuscript entitled ‘‘Characterization of TGF# -associated molecular features and drug
responses in gastrointestinal adenocarcinoma’’ by Zhang et al.  provide a comprehensive
analysis of the TGF# superfamily molecules in GIAD. The topic is interesting since TGF#
plays an important role in tumor progression, and it trigger us to know more about the TGF#
superfamily signature in the progression and treatment of GIAD. The finding is also important as
it analyzed the TGF# signature in different types of GIAD, and predicted some anti-tumor drugs
which might be useful in the therapy. However, several descriptions and interpretations for their
finding are not accurate and unclear in the text.  I suggest the text be revised as following
1. TGF# superfamily or TGF#-related molecules is not TGF#,  t.ex. line 29 in Abstract ‘‘
the molecular characterization of TGF# in GIAD’’ is not accurate. There are several similar
description in the text, and need to be carefully revised.
2. These is no methods in the Abstract, and good to have it to understand the results.
3.  The conclusions in the Abstract in line 39 are not accurate according to the findings in the
paper.
4. Line 50    Should be ‘‘all types of GIADs share the same features’’
5. Which method is used to select the significant gene mutation?
6. Line322   Top 10 genes used in DNN model are the first top 10 genes in Figure 3a? if not,
should describe them in the text.
7. Line 350-351   miRNAs and mRNAs are interpretated in an opposite way?
8. Discussion in Line 357,  ‘‘ Several drugs suggested a great sensitivity to TGF#‘‘,  what are
these drugs and their target should be discussed, since they are findings in this paper.
Similarly in Line 358 , ‘‘ some classic oncogenes were found to be targeted‘‘, what are those
oncogenes should be discussed.
9.  Line367,   The description ‘‘ with inhibiting proteins downregulated‘‘ is unclear, what are
these inhibiting
proteins?
9. Line 371,  abbreviation  ‘‘ SCNA ’’ was not described in the text.
10. Line 372-376  ‘‘which might produce more neoantigen that can be targeted at’’ is not
accurately interpreted and the following discussion about TGF#low is  unclear.
Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 4 Date: 24 Feb 2021
Reviewer's report:
The manuscript entitled ‘‘Characterization of TGF# -associated molecular features and drug
responses in gastrointestinal adenocarcinoma’’ by Zhang et al.  provide a comprehensive
analysis of the TGF# superfamily molecules in GIAD. The topic is interesting since TGF#
plays an important role in tumor progression, and it trigger us to know more about the TGF#
superfamily signature in the progression and treatment of GIAD. The finding is also important as
it analyzed the TGF# signature in different types of GIAD, and predicted some anti-tumor drugs
which might be useful in the therapy. However, several descriptions and interpretations for their
finding are not accurate and unclear in the text.  I suggest the text be revised as following
1. TGF# superfamily or TGF#-related molecules is not TGF#,  t.ex. line 29 in Abstract ‘‘
the molecular characterization of TGF# in GIAD’’ is not accurate. There are several similar
description in the text, and need to be carefully revised.
2. These is no methods in the Abstract, and good to have it to understand the results.
3.  The conclusions in the Abstract in line 39 are not accurate according to the findings in the
paper.
4. Line 50    Should be ‘‘all types of GIADs share the same features’’
5. Which method is used to select the significant gene mutation?
6. Line322   Top 10 genes used in DNN model are the first top 10 genes in Figure 3a? if not,
should describe them in the text.
7. Line 350-351   miRNAs and mRNAs are interpretated in an opposite way?
8. Discussion in Line 357,  ‘‘ Several drugs suggested a great sensitivity to TGF#‘‘,  what are
these drugs and their target should be discussed, since they are findings in this paper.
Similarly in Line 358 , ‘‘ some classic oncogenes were found to be targeted‘‘, what are those
oncogenes should be discussed.
9.  Line367,   The description ‘‘ with inhibiting proteins downregulated‘‘ is unclear, what are
these inhibiting
proteins?
9. Line 371,  abbreviation  ‘‘ SCNA ’’ was not described in the text.
10. Line 372-376  ‘‘which might produce more neoantigen that can be targeted at’’ is not
accurately interpreted and the following discussion about TGF#low is  unclear.
Please review this paper.
user
Title: Characterization of TGF#-associated molecular features and drug responses in
gastrointestinal adenocarcinoma
Version: 4 Date: 24 Feb 2021
Reviewer's report:
The manuscript entitled ‘‘Characterization of TGF# -associated molecular features and drug
responses in gastrointestinal adenocarcinoma’’ by Zhang et al.  provide a comprehensive
analysis of the TGF# superfamily molecules in GIAD. The topic is interesting since TGF#
plays an important role in tumor progression, and it trigger us to know more about the TGF#
superfamily signature in the progression and treatment of GIAD. The finding is also important as
it analyzed the TGF# signature in different types of GIAD, and predicted some anti-tumor drugs
which might be useful in the therapy. However, several descriptions and interpretations for their
finding are not accurate and unclear in the text.  I suggest the text be revised as following
1. TGF# superfamily or TGF#-related molecules is not TGF#,  t.ex. line 29 in Abstract ‘‘
the molecular characterization of TGF# in GIAD’’ is not accurate. There are several similar
description in the text, and need to be carefully revised.
2. These is no methods in the Abstract, and good to have it to understand the results.
3.  The conclusions in the Abstract in line 39 are not accurate according to the findings in the
paper.
4. Line 50    Should be ‘‘all types of GIADs share the same features’’
5. Which method is used to select the significant gene mutation?
6. Line322   Top 10 genes used in DNN model are the first top 10 genes in Figure 3a? if not,
should describe them in the text.
7. Line 350-351   miRNAs and mRNAs are interpretated in an opposite way?
8. Discussion in Line 357,  ‘‘ Several drugs suggested a great sensitivity to TGF#‘‘,  what are
these drugs and their target should be discussed, since they are findings in this paper.
Similarly in Line 358 , ‘‘ some classic oncogenes were found to be targeted‘‘, what are those
oncogenes should be discussed.
9.  Line367,   The description ‘‘ with inhibiting proteins downregulated‘‘ is unclear, what are
these inhibiting
proteins?
9. Line 371,  abbreviation  ‘‘ SCNA ’’ was not described in the text.
10. Line 372-376  ‘‘which might produce more neoantigen that can be targeted at’’ is not
accurately interpreted and the following discussion about TGF#low is  unclear.
assistant