Title: Expression and clinical significance of CCN5 and the oestrogen receptor in advanced
breast cancer
Version: 1 Date: 28 Dec 2024
Reviewer's report:
The manuscript titled “Expression and clinical significance of CCN5 and the estrogen receptor
in advanced breast cancer” explores an important topic in breast cancer research, particularly
the roles of CCN5 and ER in the progression of advanced breast cancer (BC). The study is well-
structured, with clear objectives and comprehensive methodologies. The results are presented
systematically, and the conclusions are supported by the data. However, there are several areas
for improvement in both content and presentation.
Major Concerns
1. Clarity of the Research Hypothesis:
While the study focuses on the correlation and clinical implications of CCN5 and ER, the
hypothesis could be explicitly stated in the introduction. This would provide a stronger
foundation for the research.
2. Statistical Analysis:
• Although statistical tests are described, the manuscript lacks details about corrections for
multiple comparisons, especially given the large number of associations tested.
• Effect sizes (e.g., odds ratios or correlation coefficients) should be reported to provide context
to the statistical significance.
3. Figures and Tables:
• Figures 2 and 3 lack sufficient annotation. For instance, Figure 2 should include scale bars,
while Figure 3 requires better labeling for clarity.
• Tables summarizing clinicopathological features (e.g., Table 4) should include confidence
intervals or additional metrics to strengthen the interpretation of the findings.
• Please provide a detailed explanation of how the 130 patients included in Figure 1 were
selected. Whether there was any selection bias in the patient cohort.
4. Discussion Depth:
• The discussion could better contextualize findings within existing literature. For example, the
role of CCN5 in epithelial-mesenchymal transition (EMT) is mentioned but not sufficiently
expanded upon.
• The manuscript should address potential limitations of the study, such as the generalizability
of results to populations outside of the study cohort or the absence of mechanistic exploration.
5. Ethics and Consent:
• The manuscript mentions ethics approval and informed consent, but the description could be
more detailed, especially concerning patient recruitment and the handling of clinical samples.
6. Definition of Advanced Breast Cancer:
Please clarify the definition of advanced breast cancer in the manuscript. Typically, it includes
late-stage metastatic breast cancer.
Minor Concerns
1. Language and Grammar:
• There are minor grammatical errors and awkward phrasings throughout the manuscript. For
example, in the abstract: “High expression of CCN5 and ER were observed…” should be revised
to “High expression of CCN5 and ER was observed.”
• Ensure consistency in terminologies, e.g., “ductal carcinoma in situ” (DCIS) versus “in situ
carcinoma.”
2. Abbreviations:
• All abbreviations should be defined at their first occurrence, e.g., CCN5 (CCN family member
5).
3. Reference Formatting:
• Some references lack uniform formatting (e.g., inconsistent use of journal abbreviations).
Ensure adherence to the journal’s reference style.
4. Figure and Table Captions:
• Captions are overly brief. Add explanatory notes to make the figures and tables self-contained.
Recommendations for Improvement
1. Expand Methodological Details:
Provide additional information on sample collection and immunohistochemistry scoring criteria
to enhance reproducibility.
2. Integrate Mechanistic Insights:
If possible, include a brief discussion on how CCN5 and ER interact mechanistically, referencing
molecular pathways.
3. Improve Visuals:
Revise figures for better clarity and visual appeal. Consider using heatmaps or bar graphs to
depict the correlation analysis.
4. Address Study Limitations:
Add a section explicitly addressing limitations such as sample size and retrospective design.