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All remaining concerns of the reviewer were successfully addressed and the revised manuscript is acceptable now.
[# PeerJ Staff Note - this decision was reviewed and approved by Fanglin Guan, a PeerJ Section Editor covering this Section #]
Please address remaining concerns of the reviewers and amend manuscript accordingly.
[# PeerJ Staff Note: It is PeerJ policy that additional references suggested during the peer-review process should *only* be included if the authors are in agreement that they are relevant and useful #]
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Clinical relevance studies involve a variety of complex variables, and the sample size included in this study is very limited. As clearly shown in Table 1, RAD51 is only associated with T-stage. These limitations highlight the necessity of gene function studies. Contrary to the results of two existing studies (PMID: 36415794; PMID: 34978208), the authors should cite the literature and elaborate on the possible deeper underlying reasons in the discussion section. In addition, it is recommended that the authors provide further interpretation of pan-cancer bioinformatics analysis, which can refer to PMID: 38065270.
Please address concerns of the reviewer #3 and amend manuscript accordingly.
[# PeerJ Staff Note: It is PeerJ policy that additional references suggested during the peer-review process should *only* be included if the authors are in agreement that they are relevant and useful #]
The modified version has resolved the previous issue, and I have no other problems
The modified version has resolved the previous issue, and I have no other problems
The modified version has resolved the previous issue, and I have no other problems
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Two published studies have consistently shown that high expression of RAD51 in gastric adenocarcinoma is associated with favorable clinical outcomes and has a protective effect on genes. This is completely contrary to the findings reported by the authors of this paper. Therefore, it is essential to conduct further experimental research to address this controversy.
Redati D, Yang X, Lei C, Liu L, Ge L, Wang H. Expression and Prognostic Value of RAD51 in Adenocarcinoma at the Gastroesophageal Junction. Iran J Public Health. 2022 Oct;51(10):2231-2243. doi: 10.18502/ijph.v51i10.10981. PMID: 36415794; PMCID: PMC9647605.
(Figure 3)
Pádua JDB, Mariano CFA, Fabro AT, Tirapelli DPDC, Sankarankutty AK, Dos Santos JS, Brunaldi MO. Prognostic Value of the Immunohistochemical Expression of RAD51 and BRCA2 in Gastric Adenocarcinoma. J Histochem Cytochem. 2022 Mar;70(3):199-210. doi: 10.1369/00221554211065834. Epub 2022 Jan 3. PMID: 34978208; PMCID: PMC8832630.
(Figure 2)
The authors state that RAD51 protein expression is only significantly correlated with T stage in Table 1. Given that this is a single-gene study, I strongly recommend including experimental data on the proliferation/migration/invasion phenotypes of STAD cells before and after RAD51 overexpression or knockdown.
Two published studies have consistently shown that high expression of RAD51 in gastric adenocarcinoma is associated with favorable clinical outcomes and has a protective effect on genes. This is completely contrary to the findings reported by the authors of this paper. Therefore, it is essential to conduct further experimental research to address this controversy.
Redati D, Yang X, Lei C, Liu L, Ge L, Wang H. Expression and Prognostic Value of RAD51 in Adenocarcinoma at the Gastroesophageal Junction. Iran J Public Health. 2022 Oct;51(10):2231-2243. doi: 10.18502/ijph.v51i10.10981. PMID: 36415794; PMCID: PMC9647605.
(Figure 3)
Pádua JDB, Mariano CFA, Fabro AT, Tirapelli DPDC, Sankarankutty AK, Dos Santos JS, Brunaldi MO. Prognostic Value of the Immunohistochemical Expression of RAD51 and BRCA2 in Gastric Adenocarcinoma. J Histochem Cytochem. 2022 Mar;70(3):199-210. doi: 10.1369/00221554211065834. Epub 2022 Jan 3. PMID: 34978208; PMCID: PMC8832630.
(Figure 2)
The authors state that RAD51 protein expression is only significantly correlated with T stage in Table 1. Given that this is a single-gene study, I strongly recommend including experimental data on the proliferation/migration/invasion phenotypes of STAD cells before and after RAD51 overexpression or knockdown.
Please address issues pointed out by the reviewers and revise manuscript accordingly.
[# PeerJ Staff Note: It is PeerJ policy that additional references suggested during the peer-review process should *only* be included if the authors are in agreement that they are relevant and useful #]
1. It is recommended that the authors add a flow chart of the whole study.
2. Outdated references cited, especially in the Introduction. Additionally, it is essential to cite original literature rather than relying on secondary sources for references.
3. Lack of ethical statements.
The study would benefit from experimental validation. Including in vitro or in vivo experiments to confirm the role of identified RAD51 in the STAD would strengthen the evidence.
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This manuscript describes the expression and prognostic value of RAD51 in gastric adenocarcinoma using bioinformatics and immunohistochemistry. Although it lacks innovation, the manuscript is overall well written and doesn't seem to be a fishing expedition. However, there are still some shortcomings in this work and several sections need further improvement. The manuscript needs a major revision before publication.
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1. There have been some reports on RAD51 and gastric cancer (such as PMID: 36415794, PMID: 34978208, PMID: 35359409) that are worthy of the author's attention and cannot be ignored. Similar reports should be added or updated in the introduction and discussion of the manuscripts.
2. The information in the conclusion is too brief to reflect the value of RAD51 in immunity. The same problem occurs in the title, which does not reflect the immunity information.
3. The manuscript focuses on the value of RAD51 in the prognosis of STAD, but there are few related results that can be appropriately complemented, such as ROC curve and related prognostic model.
4. Bioinformatics methods are too simple and should be supplemented and improved accordingly.
In this study, the authors use public databases and tissue chip data to attempt to elucidate the differential expression, clinical relevance, and diagnostic value of RAD51 in stomach adenocarcinoma (STAD) and adjacent normal tissues. However, I find that this manuscript lacks depth and presents rather basic findings. Below are my detailed comments:
1.Figure 2A: The data is generated using the TIMER web tool, not the GEPIA database as the authors mention. Since this study focuses on a single cancer type, stomach adenocarcinoma, the authors should justify why it is necessary to present the pan-cancer analysis of RAD51 mRNA expression. If the authors believe this is necessary, then they should also include the pan-cancer protein expression differences in Figure 2C, not just RAD51 expression in STAD.
2.As the sole original experimental data in this study, the results of the tissue chip staining of 90 cancer and adjacent normal samples should be presented as panoramic scans in the supplementary materials. Additionally, the IHC quantification and clinicopathological data for each patient should be provided.
3.Figure 3B: Please add the statistical p-value for the Kaplan-Meier curve.
4.Figure 4: The authors should explain the screening strategy for the RAD51 co-expression network, or clarify why only eight genes were highlighted. What about the correlation of other co-expressed genes? These correlations are based solely on mRNA expression levels. Given that the authors conducted IHC and quantification, it is essential to also provide the protein expression level correlations.
5.Since the study emphasizes the diagnostic significance of RAD51, the authors should include additional analyses, such as the prediction efficiency of RAD51 in cancer diagnosis and prognosis, including the ROC curve.
6.Supplementary Figure 1: The relevance of showing the correlation between RAD51 and six types of immune cell infiltration using the TIMER database is unclear. The results do not present strong correlations, as none of the coefficients exceed 0.4. Since other co-expressed genes are already strongly positively correlated with RAD51, it is expected that they would show similar results to RAD51. The authors should clarify the significance of these findings.
7.The authors state that RAD51 protein expression is only significantly correlated with T stage in Table 1. Given that this is a single-gene study, I strongly recommend including experimental data on the proliferation phenotypes of STAD cells before and after RAD51 knockdown.
8.The co-expression analysis shows that RAD51 is closely related to cell cycle genes. Therefore, the authors should supplement the study with experimental data on the effects of RAD51 on the cell cycle in STAD cells, possibly through techniques such as flow cytometry.
9.The manuscript needs systematic language polishing and formatting adjustments, such as maintaining consistency in how RAD51 and Rad51 are written throughout the text.
10. The introduction should better summarize the current research progress and gaps concerning RAD51 in STAD, while the discussion should highlight the novel findings of this study and how they could guide future research or clinical therapy.
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