Comprehensive Analysis of Mutation-Based and Expressed Genes-Based Pathways in Head and Neck Squamous Cell Carcinoma
, Jin-Young Park 2, Jin-Pyo Kim 2, Gun-Do Kim 2, Yun-Suk Yu 2, Sang-Hee Cho 3, Sangwoo Kim 4, Hee-Kyung Ahn 5, Sang-Hoon Chun 6, Jung-Hye Kwon 7, Tak Yun 8, Ji-Won Kim 9, Ji-Eun Kim 10, Myung-Ju Ahn 11, Joo-Hang Kim 12 and Hwan-Jung Yun 13,*Round 1
Reviewer 1 Report
The paper is an interesting study describing a novel approach to integrate DNA mutational data and mRNA expression patterns into the protein-protein interactions network pathways, for matching potential drug or druggable pathways.For this study, 93 recurrent/metastatic HNSCC patients have been enrolled and targeted gene sequencing together with mRNA expression has been performed. Mutational and nanostring data have been investigated using the CBSJukebox® system, while, to identify appropriate drugs, Treatment Benefit Prediction Score (TBPS) has been calculated. The work is well written and structured. The conclusions are clearly stated. Although this study has been developed in silico and validated only in two HNSCC patients, the results are of clear importance in the field and provide some promising therapeutical perspectives for HNSCC.
Author Response
Thank you for your insightful and kind comments. We agree with your comment, and we also hope that we can validate in a future study.
Reviewer 2 Report
In this study, Keam and colleagues investigated the pathways in head and neck squamous cell carcinoma (HNSCC) by a bioinformatic approach. The authors found that immune checkpoint inhibitors, EGFR inhibitors, and FGFR inhibitors might be beneficial to cancer treatment. The drugs the authors mentioned are already being used for the treatment of squamous cell carcinoma in the clinic. The manuscript, therefore, does not add anything new to the field. I believe the authors may make a more significant discovery if they can analyze or generate HNSCC single-cell sequencing data.
Author Response
Thank you for your insightful comments
1) The authors found that immune checkpoint inhibitors, EGFR inhibitors, and FGFR inhibitors might be beneficial to cancer treatment. The drugs the authors mentioned are already being used for the treatment of squamous cell carcinoma in the clinic. The manuscript, therefore, does not add anything new to the field.
authors' response to review>
Immune checkpoint inhibitor is already introduced to the treatment of head and neck squamous cell carcinoma. However, EGFR inhibitor poziotinib, and FGFR inhibitor nintedanib is not yet approval because of lack of companion diagnostics. Hence we believe that our approach can provide guidance and treatment decision for targeted agents.
2) I believe the authors may make a more significant discovery if they can analyze or generate HNSCC single-cell sequencing data.
authors' response to review>
Thank you for valuable comment. We agree with your opinion. However, we did not collect patients blood and most patients are already dead. Even though we can not do single cell sequence in this study, we will consider single cell sequencing for next future study.
