Next Article in Journal
Coordinated Expression of Ras Suppressor 1 (RSU-1) and Growth Differentiation Factor 15 (GDF15) Affects Glioma Cell Invasion
Next Article in Special Issue
Should Tumor Infiltrating Lymphocytes, Androgen Receptor, and FOXA1 Expression Predict the Clinical Outcome in Triple Negative Breast Cancer Patients?
Previous Article in Journal
A Novel Type of Blood Biomarker: Distinct Changes of Cytokine-Induced STAT Phosphorylation in Blood T Cells Between Colorectal Cancer Patients and Healthy Individuals
Previous Article in Special Issue
EV-Associated miRNAs from Peritoneal Lavage are a Source of Biomarkers in Endometrial Cancer
 
 
Article
Peer-Review Record

A Tyrosine Kinase Expression Signature Predicts the Post-Operative Clinical Outcome in Triple Negative Breast Cancers

Cancers 2019, 11(8), 1158; https://doi.org/10.3390/cancers11081158
by Alexandre de Nonneville 1, Pascal Finetti 2, José Adelaide 2, Éric Lambaudie 3, Patrice Viens 1, Anthony Gonçalves 1, Daniel Birnbaum 2, Emilie Mamessier 2 and François Bertucci 1,2,*
Reviewer 1: Anonymous
Reviewer 2: Anonymous
Cancers 2019, 11(8), 1158; https://doi.org/10.3390/cancers11081158
Submission received: 15 July 2019 / Revised: 4 August 2019 / Accepted: 9 August 2019 / Published: 13 August 2019
(This article belongs to the Special Issue New Insights into Breast and Endometrial Cancer)

Round 1

Reviewer 1 Report

This paper describes the development of a 13-gene expression signature as a prognostic tool for triple-negative breast cancer patients. The discovery method uses a fairly straightforward statistical approach. The rationale for focusing on genes that express TKs is not entirely clear, since it is TK activation, not gene expression, that drives oncogenesis. Nevertheless, there are clear examples (e.g. HER2) where overexpression is a major cause of oncogenic activity, and the authors’ approach yields a prognostic panel derived from a >800-patient discovery set, that performs well on a >400-patient validation set. Whether, as suggested in the Conclusion, there are therapeutic implications, is entirely speculative at this stage. 

 

Specific points

 

1. The authors will be aware that the six Lehmann TNBC subtypes are now re-classified into 4 subtypes (PMID: 27310713), reflecting in part that the immunomodulatory subtype largely describes gene expression from infiltrating lymphocytes. This should be included in the Introduction and Discussion. Since the 13-gene signature is strongly correlated with immunity-related signatures, to what extent is its prognostic performance simply reflecting the well-established observation that a high tumor immune infiltration, in particular CD8 TILs, is prognostic for better survival?

 

2. Most of the data are derived from microarrays. When allocating the 1226 TNBC samples between discovery and validation groups, how were the RNA-Seq-derived data distributed between the two groups?  

 

3. Was the gene signature also tested against overall survival?


Author Response

Reply to the Review Report is attached as a word document

Author Response File: Author Response.docx

Reviewer 2 Report

In the present manuscript, Alexandre DE Noneville et al. used 1226 TNBC patients’ mRNA and histoclinical data, searched TK-based GES associated with DFS and then tested its robustness. They finally identified 13 TK GESs associated with DFS in TNBC patients and could be a better prognostic marker in TNBC patiens. This is an interesting study and a well conducted one. I appreciate the study design and the observations made during the study. However, there are some questions are still needed to be clarified.


1. How to utilize the authors’ findings to clinical application? Most of the tumors were high grade (81% of grade 3), therefore, surgery followed by adjuvant chemotherapy should be a standard of treatment for locally advanced BC. Is there any correlation among these different drug responses and 13 TK-associated genes, immunity-related signatures, MHC class I/II antigen presentation pathways and immune cells infiltration? 


2. The authors did not show the direct evidences by cell or animal model to proof their findings. 


3. The present manuscript lacks the immunohistochemistry staining for further verification


Minor:

The abstract should be written in one paragraph.


Author Response

Reply to the Review Report is attached as a word document

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The authors have made satisfactory improvement in response to the reviewers' comments and suggestions.

Back to TopTop