Expression of AKT1 Related with Clinicopathological Parameters in Clear Cell Renal Cell Carcinoma
Round 1
Reviewer 1 Report
Authors analyzed the clinicopathologic features between clear cell RCC with different AKT1 expression levels and the correlation with clinical outcomes/behaviors. It is an interesting study. Some points authors should address are:
1. Various studies have observed increased Akt activities in different malignant tumors, including clear cell RCC. A disruption of Akt activation has been shown to inhibit cell proliferation and therefore has been considered to be a potentially novel therapeutic strategy. However, very interestingly, authors showed that high AKT expressing ccRCCs had longer recurrence-free survival and progression-free survival. Authors need to discuss it in "Dicussion".
2. Authors used "high expression of AKT1" and "low expression of AKT1" throughout the text. To avoid , it would be better to show what the expression level compared to. Is it compared to normal kidney tissue? It would be better to show H-score of normal kidney tissue, high expression group and low expression group.
3. In abstract, the usage of clear cell type kidney tumor is improper. It should use the correct term, clear cell renal cell carcinoma.
4. In Material and methods, line 59, AJCC is tumor staging system, rather than a tumor grading system. Clear cell renal cell carcinoma is graded using WHO/ISUP grading criteria currently. Fuhrman grade is not recommended.
5. Abstract need to modify to highlight their findings better. For example, three public database rather "three public data", emphasizing the results, ...
Author Response
Dear,
Please check the attached file.
We did our best to refine the article.
Best regards,
Author Response File: 
Author Response.docx
Reviewer 2 Report
General comments to the paper entitled
Expression of AKT1 related with …
The authors used two mouse model datasets and a human dataset to investigate the expression pattern of mTOR-associated genes from clear cell renal cell carcinoma (RCC). The data of the three datasets were compared and visualized.
The authors collected tissue samples from 58 clear cell RCC patients and the AKT1 expression was evaluated with immunohistochemical staining. The goal was to analyze the AKT1 gene regulation and find a correlation with survival.
Figure 1-2-3 shows the relative expression levels of mTOR-associated genes of data of mouse-human-mouse getting from datasets. I suggest changing the order: mouse-mouse-human.
Fig. 4.: Please check the magnification of A and B. It seems to me that the A is x200 and B is x400.
The data confirm the higher AKT1 expression coupled with longer recurrence-free and progression-free survival.
Author Response
Dear,
Please check the attached file.
We did our best to refine the article.
Best regards,
Author Response File: Author Response.docx
Reviewer 3 Report
The paper presented by Choi and colleagues presents poor results and needs further experiments in order to improve and consolidate the work presented. More experiments are needed in order to understand how AKT1 expression may influence the prognosis. It would be advisable to evaluate the phosphorylation status of AKT1 in patients, and also to evaluate the expression of other proteins in the AKT1 network. Besides that, there are other doubts that should be clarified:
- Why did the authors decide to consider datasets from mice and correlate them with datasets from humans? Also the dates of access made to the various datasets are absent from the materials and methods .
- The datasets used have different phenotypes (WT vs mutant for example), the authors should comment on the results obtained for AKT1 expression also in light of these issues.
- For immunohistochemistry analysis, the machine used for image acquisition is missing in the materials and methods. The calibration bars are missing in the images, and it would be useful to have a table with the scores obtained in the various analysis and a graphical representation of the results using histograms.
- It would be useful to divide the results paragraph into two by dividing the bioinformatics analysis of the datasets, from the analysis of the patient-reported data.
- In the discussion of the results, the authors should better discuss their results as they represent very few lines compared to the whole paragraph, so the discussion should be improved.
- Lastly, references should be no older than 10 years.
Author Response
Dear,
Please check the attached file.
We did our best to refine the article.
Best regards,
Author Response File: Author Response.docx
Round 2
Reviewer 3 Report
The text still has errors: there are grammatical errors in the text, and also some information are still missing in the materials and methods. In particular, the review board statement and information regarding informed consent are missing.
Authors also did not include graphs regarding AKT1 expression results obtained by immuhistochemistry.
Author Response
Reviewer 3:
The text still has errors: there are grammatical errors in the text, and also some information are still missing in the materials and methods. In particular, the review board statement and information regarding informed consent are missing.
Answer:
Thanks for the reviewer's comments.
The authors carried out the work of the article through an official English proofreading company. Of course, there may be some awkward parts while making some article corrections. If a reviewer points out an awkward part, we will correct it.
A review board statement and information regarding informed consent are described below at the bottom of the article.
In manuscript:
Institutional Review Board Statement: The studies involving human participants were reviewed and approved by the Institutional Review Board of Kyung Hee University Hospital at Gangdong (KHNMC- 2014-11-044).
Informed Consent Statement: Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
Authors also did not include graphs regarding AKT1 expression results obtained by immuhistochemistry.
.
Answer:
Thanks for detailed comments. At the request of the reviewer, the graph and results have been added as follows.
In manuscript:
Graphs according to 58 clear cell renal cell carcinoma tissues regarding AKT1 expression intensity and proportion results obtained by immunohistochemistry are shown (Figure 5).
Figure 5. Graphs according to intensity and proportion regarding AKT1 expression results obtained by immunohistochemistry.
Author Response File: Author Response.docx
