Reviewer ’s report  
 
Title:  FBXW7 expression is associated with prognosis and chemotherapeutic outcome in 
Chinese patients with gastric adenocarcinoma  
 
Version: 0 Date: 18 Apr 2016 
 
Reviewer:  Marco  Pizzi  
 
Reviewer’s report:  
 
In this paper, Li and colleagues investigate the expression of FBXW7 in a large series of gastric 
adenocarcinomas by mRNA (28 cases) a nd immunohistochemical analysis (546 cases). They 
demonstrate different expression levels of this protein and correlate such differences with several 
clinical and pathological parameters. In particular, they find that high FBXW7 expression is 
ossociated wi th better OS (this is particularly true for stage III cases). They also show that these 
differences are maintained in cohorts of patients treated with paclitaxel and/or platinum, but are 
no longer present when only anthracycline -treated patients are consid ered. The study is 
interesting and globally well done. Some points need however to be further addressed.  
 
 
Major concerns:  
 
1) The interpretation of OS results based on FBXW7 levels and adjuvant CT does not seem 
formally correct and is largely misleading. In several passages (Results and Discussion sections), 
the Authors report sentences like: "high FBXW7 expression is associat ed with better outcome for 
those treated with paclitaxel or platinum", while "there was no significant difference between the 
two groups treated by anthracycline". This and similar sentences are misleading, as shown in 
Figure 5: according to this figure, h igh FBXW7 expression is indeed associated with better OS 
irrespective of paclitaxel and/or platinum treatment (i.e. similar results are obtained in both 
platinum and/or paclitaxel treated and untreated patients). As for anthracycline, differences in OS 
are significant only for those who have not been treated with this drug. Thus, the Authors' 
conclusions need to be changed, as they imply that high FBXW7 expression can stratify patients 
who will respond to paclitaxel and/or platinum (see last sentence of the  Discussion), but this is 
not the case.  
 
2) What about FBXW7 expression and prognostic value according to the specific gastric cancer 
type (intestinal versus diffuse)?  
 
 
Minor points:  
 
1) Introduction (and Discussion): it is reported that FBXW7 is expressed in several human 
tumors, despite the present paper focuses on its down -regulation as a prognostic factor. This is 
not necessarily a discrepancy, but a comment in the Discussion and more literature data are 
probably needed to clarify the role of FBXW7 in hu man tumors.  
2) Materials and Methods, TMA construction section: what does "at fixed point" mean?  
 
3) Materials and Methods, IHC techniques section: what dilution and clones were used for 
the anti -FBXW7 antibody?  
 
4) Results: what does "18s" stand for (first page of the Results, line 22)?  
 
5) Results: details on IHC results are needed. How were cases distributed according to each 
IHC score? A table reporting such data may be helpful.  
 
6) First page of the results, line 41 -48: this passage could be clearer. If I understand 
correctly, the OS in the whole study population correlated with FBXW7 expression, but (when 
analyzed by stage) such significancy only remained for stage III patients. I suggest rephrasing.  
 
7) Discussion, second page line 3: I suggest changing th e expression "union 
chemoterapeutics". Immediatly thereafter, the paragraph analyzing possible correlations between 
FBXW7 and CT resistance is very interesting, but not very clear. I suggest rephrasing it in a 
more direct way.  
 
8) A higher magnification for  histologic images may help better appreciate the expression of 
FBXW7. Which controls were used to assess the quality of such reaction? How was the 
expression pattern within tumor cells?  
 
9) Table 2: Please change "N classification" and "T classification" w ith "N stage" and "T 
stage", respectively  
 
10) There are several typo errors that need to be corrected. The English form could also be 
improved (mostly in the Introduction). I also suggest not reporting twice the same data in the 
Materials & Methods and Res ults: some of the Result paragraphs could be shortened.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I am a ble to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in a n organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimb ursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
No competing interests to declare  
 
I agree to the open peer review po licy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
respons es. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish t o be included in my named report can be included as confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title:  FBXW7 expression is associated with prognosis and chemotherapeutic outcome in 
Chinese patients with gastric adenocarcinoma  
 
Version: 0 Date: 18 Apr 2016 
 
Reviewer:  Marco  Pizzi  
 
Reviewer’s report:  
 
In this paper, Li and colleagues investigate the expression of FBXW7 in a large series of gastric 
adenocarcinomas by mRNA (28 cases) a nd immunohistochemical analysis (546 cases). They 
demonstrate different expression levels of this protein and correlate such differences with several 
clinical and pathological parameters. In particular, they find that high FBXW7 expression is 
ossociated wi th better OS (this is particularly true for stage III cases). They also show that these 
differences are maintained in cohorts of patients treated with paclitaxel and/or platinum, but are 
no longer present when only anthracycline -treated patients are consid ered. The study is 
interesting and globally well done. Some points need however to be further addressed.  
 
 
Major concerns:  
 
1) The interpretation of OS results based on FBXW7 levels and adjuvant CT does not seem 
formally correct and is largely misleading. In several passages (Results and Discussion sections), 
the Authors report sentences like: "high FBXW7 expression is associat ed with better outcome for 
those treated with paclitaxel or platinum", while "there was no significant difference between the 
two groups treated by anthracycline". This and similar sentences are misleading, as shown in 
Figure 5: according to this figure, h igh FBXW7 expression is indeed associated with better OS 
irrespective of paclitaxel and/or platinum treatment (i.e. similar results are obtained in both 
platinum and/or paclitaxel treated and untreated patients). As for anthracycline, differences in OS 
are significant only for those who have not been treated with this drug. Thus, the Authors' 
conclusions need to be changed, as they imply that high FBXW7 expression can stratify patients 
who will respond to paclitaxel and/or platinum (see last sentence of the  Discussion), but this is 
not the case.  
 
2) What about FBXW7 expression and prognostic value according to the specific gastric cancer 
type (intestinal versus diffuse)?  
 
 
Minor points:  
 
1) Introduction (and Discussion): it is reported that FBXW7 is expressed in several human 
tumors, despite the present paper focuses on its down -regulation as a prognostic factor. This is 
not necessarily a discrepancy, but a comment in the Discussion and more literature data are 
probably needed to clarify the role of FBXW7 in hu man tumors.  
2) Materials and Methods, TMA construction section: what does "at fixed point" mean?  
 
3) Materials and Methods, IHC techniques section: what dilution and clones were used for 
the anti -FBXW7 antibody?  
 
4) Results: what does "18s" stand for (first page of the Results, line 22)?  
 
5) Results: details on IHC results are needed. How were cases distributed according to each 
IHC score? A table reporting such data may be helpful.  
 
6) First page of the results, line 41 -48: this passage could be clearer. If I understand 
correctly, the OS in the whole study population correlated with FBXW7 expression, but (when 
analyzed by stage) such significancy only remained for stage III patients. I suggest rephrasing.  
 
7) Discussion, second page line 3: I suggest changing th e expression "union 
chemoterapeutics". Immediatly thereafter, the paragraph analyzing possible correlations between 
FBXW7 and CT resistance is very interesting, but not very clear. I suggest rephrasing it in a 
more direct way.  
 
8) A higher magnification for  histologic images may help better appreciate the expression of 
FBXW7. Which controls were used to assess the quality of such reaction? How was the 
expression pattern within tumor cells?  
 
9) Table 2: Please change "N classification" and "T classification" w ith "N stage" and "T 
stage", respectively  
 
10) There are several typo errors that need to be corrected. The English form could also be 
improved (mostly in the Introduction). I also suggest not reporting twice the same data in the 
Materials & Methods and Res ults: some of the Result paragraphs could be shortened.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I am a ble to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in a n organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimb ursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
No competing interests to declare  
 
I agree to the open peer review po licy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
respons es. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish t o be included in my named report can be included as confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title:  FBXW7 expression is associated with prognosis and chemotherapeutic outcome in 
Chinese patients with gastric adenocarcinoma  
 
Version: 0 Date: 18 Apr 2016 
 
Reviewer:  Marco  Pizzi  
 
Reviewer’s report:  
 
In this paper, Li and colleagues investigate the expression of FBXW7 in a large series of gastric 
adenocarcinomas by mRNA (28 cases) a nd immunohistochemical analysis (546 cases). They 
demonstrate different expression levels of this protein and correlate such differences with several 
clinical and pathological parameters. In particular, they find that high FBXW7 expression is 
ossociated wi th better OS (this is particularly true for stage III cases). They also show that these 
differences are maintained in cohorts of patients treated with paclitaxel and/or platinum, but are 
no longer present when only anthracycline -treated patients are consid ered. The study is 
interesting and globally well done. Some points need however to be further addressed.  
 
 
Major concerns:  
 
1) The interpretation of OS results based on FBXW7 levels and adjuvant CT does not seem 
formally correct and is largely misleading. In several passages (Results and Discussion sections), 
the Authors report sentences like: "high FBXW7 expression is associat ed with better outcome for 
those treated with paclitaxel or platinum", while "there was no significant difference between the 
two groups treated by anthracycline". This and similar sentences are misleading, as shown in 
Figure 5: according to this figure, h igh FBXW7 expression is indeed associated with better OS 
irrespective of paclitaxel and/or platinum treatment (i.e. similar results are obtained in both 
platinum and/or paclitaxel treated and untreated patients). As for anthracycline, differences in OS 
are significant only for those who have not been treated with this drug. Thus, the Authors' 
conclusions need to be changed, as they imply that high FBXW7 expression can stratify patients 
who will respond to paclitaxel and/or platinum (see last sentence of the  Discussion), but this is 
not the case.  
 
2) What about FBXW7 expression and prognostic value according to the specific gastric cancer 
type (intestinal versus diffuse)?  
 
 
Minor points:  
 
1) Introduction (and Discussion): it is reported that FBXW7 is expressed in several human 
tumors, despite the present paper focuses on its down -regulation as a prognostic factor. This is 
not necessarily a discrepancy, but a comment in the Discussion and more literature data are 
probably needed to clarify the role of FBXW7 in hu man tumors.  
2) Materials and Methods, TMA construction section: what does "at fixed point" mean?  
 
3) Materials and Methods, IHC techniques section: what dilution and clones were used for 
the anti -FBXW7 antibody?  
 
4) Results: what does "18s" stand for (first page of the Results, line 22)?  
 
5) Results: details on IHC results are needed. How were cases distributed according to each 
IHC score? A table reporting such data may be helpful.  
 
6) First page of the results, line 41 -48: this passage could be clearer. If I understand 
correctly, the OS in the whole study population correlated with FBXW7 expression, but (when 
analyzed by stage) such significancy only remained for stage III patients. I suggest rephrasing.  
 
7) Discussion, second page line 3: I suggest changing th e expression "union 
chemoterapeutics". Immediatly thereafter, the paragraph analyzing possible correlations between 
FBXW7 and CT resistance is very interesting, but not very clear. I suggest rephrasing it in a 
more direct way.  
 
8) A higher magnification for  histologic images may help better appreciate the expression of 
FBXW7. Which controls were used to assess the quality of such reaction? How was the 
expression pattern within tumor cells?  
 
9) Table 2: Please change "N classification" and "T classification" w ith "N stage" and "T 
stage", respectively  
 
10) There are several typo errors that need to be corrected. The English form could also be 
improved (mostly in the Introduction). I also suggest not reporting twice the same data in the 
Materials & Methods and Res ults: some of the Result paragraphs could be shortened.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I am a ble to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in a n organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimb ursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
No competing interests to declare  
 
I agree to the open peer review po licy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
respons es. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish t o be included in my named report can be included as confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
assistant