Differential Gene Expression and Methylation Analysis of Melanoma in TCGA Database to Further Study the Expression Pattern of KYNU in Melanoma

Round 1

Reviewer 1 Report

The authors have adequately addressed the concerns raised by the reviewer. Thank you

Reviewer 2 Report

The manuscript has already been extensively revised - thank you for including all remarks.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

Overall, the study idea is interesting, and the work could have merit in the related field. Just very few concerns should be addressed

General comments

- The authors should ensure that all gene names are italicized to match the standards of HUGO for gene nomenclatures and differentiate it from the protein nomenclature “non italicized”.

Specific comments

1- The introduction section is very long. It should be revised and be specific to the point.

2- The specific cause behind the selection of the KYNU gene, among others, to assess its expression was unclear, especially by the end of the introduction and in the “Methods” section.

3- The “Immunohistochemistry” section included a mix of paragraphs with passive voice and active one (e.g. Wash 3 times with PBS for 5 min; add 4…., place……., ..etc.)

4- The figures that consist of more than one panel, the authors should elaborate for each panel separately in the figure legend to be clear for the reader.

Reviewer 2 Report

In this study, the authors investigated the expression and methylation profile in melanoma using TCGA dataset. In addition, Wang et al explored the potential role of KYNU in melanoma aggressiveness. The work presented by Wang and co-workers seems to be two distinct works. The first part is a bioinformatic approach using the TCGA database to explore the differential expressed genes in melanoma, as well as the gene methylation, CNV and mutation profiles. They provided 8 figures to shown data that has been reported is several published manuscripts. Moreover figure 1, 2, 4 and 7 are not original data and are more appropriated for a review article. These data could be of interest if focused in showing a pattern or gene signature associated with some features of melanogenesis or clinical data. I was expecting to see KYNU altered in the bioinformatic analysis not only to justify this first analysis but also as as a starting point to explain why the authors decided to explore the role of KYNU in melanoma. I can not see a rational between the “two” parts of the work. Moreover, the authors seems not to have a particular care about how the figures are presented (just some print screens). The authors should also provide more complete figure legends highlighting what they want to show.

The “second” part of the work is more interesting and although some of the findings may be interesting, the way they are described and present need to be improved and refined. Again the authors provide aditional 11 Figures. The amount of figures is enormous and the authors should focus in showing what is new and provide only 6 to 8 figures maximum (not 19 Figures). Here, Wang and co-workers performed IHC and functional assays to demonstrate the functional role of KYNU is melanoma. The HPA analysis should be removed from the manuscript. It does not provide any additional information. The authors should perform clinical correlations with their own melanoma cohort to assess KYNU as a potential biomarker. The rational behind KYNU, IL10, IFN is not clear and need further clarifications. The last results of this manuscript (section 3.9) are just literature description and no original work is provided.

 

Overall the manuscript text needs major English and grammar error corrections. The way the results and figures are presented makes it difficult to readers and should be improved. Beside that, several issues arise regarding the analysis that has been provided as well as the interpretation of some results.

Please provide figures/results clear and strait to the point. The results and the discussion need also major alterations, the conclusions of the authors are not totally supported by the results.

Reviewer 3 Report

The manuscript contains numerous flaws that disqualifies it for the acceptance in the Journal of Personalized Medicine. The manuscript is written in a very chaotic way, containing many typos and substantive errors. 

The Abstract and Intoduction are too long and contain a lot of unnecessary information (eg lines 46-51 in the Introduction). Half of this manuscript could be rewritten and submit as a nice review on melanoma pathology. Most results and conclusions are already widely known and bear no novelty.

Figure 1 and Figure 2 from page 4 iare not included in the text. Moreover, the Results section restarts figure numbering. Please rearrange the Figure numbering throughout the whole manuscript. Are these figures prepared by the Authors from the scratch? If not, the source of all figures not prepared from Authors should be added.

All the programming scripts should be added in supplementary materials and methods, or added to a GitHub repository (or similar one). Then, only the link to the repository sould be included in the manuscript. All the comments to the script should be also translated from Chinese into English.

Some results and conclusions are dubious. For instance, the authors claim that PTEN is highly elevated in melanoma cells, whereas it is widely recognized that PTEN is a tumor suppressor frequently lost in melanoma.

Most of materials and method section are written as copy-paste from manuals or protocols, without even changing the tenses.

Super- and subscripts are not formatted (eg H2O2 on line 251 or 106 cells on line 329), gene abbreviations are not unified (eg BRAF vs B-RAF), and numerous typos are present (eg. symble and Ensymble, verafinib instead of vemurafenib etc.)