The Association between Human Epididymis Secretory Protein 4 and Metabolic Syndrome
Round 1
Reviewer 1 Report
This study investigates the potential relationship between metabolic syndrome and epididymal protein 4 levels. The topic is of interest and the study setup appropriate.
Some points can be modified or improved:
- the sentence in line #58 is not complete
- it would be good to, in table 2, include first the coefficients of all individual parameters, i.e. age, for model 1 and then describe that the influence of these specific parameters on HE4 levels is corrected for in model 2.
- although the authors already mentioned that the use of only females is is a limitation of the study, it would be good to explain (i.e. in the methods section) why males could not be included in the analysis.
Author Response
Point 1: the sentence in line #58 is not complete
Response 1: Thank you for your constructive critique. We have revised the sentence to “Therefore, HE4 overexpression is associated with a worse prognosis for epithelial ovarian carcinoma (EOC).” (Page 2, line 58-59)
Point 2: it would be good to, in table 2, include first the coefficients of all individual parameters, i.e. age, for model 1 and then describe that the influence of these specific parameters on HE4 levels is corrected for in model 2.
Response 2: Thank you for your constructive critique. We have revised the manuscript as your suggestion into our Results part. “Table 2 shows the regression coefficients of the presence and number of metabolic syndrome components for HE4 level. There were influence of individual parameters on HE4 levels in model 1, such as age, race/ethnicity, BMI, serum AST and creatinine, history of CAD, and cigarette smoking. We adjusted for these covariates in model 2.” (Page 4, line 136-140)
Point 3: although the authors already mentioned that the use of only females is a limitation of the study, it would be good to explain (i.e. in the methods section) why males could not be included in the analysis.
Response 3: Thank you for your constructive critique. We have revised the manuscript as your suggestion into our Materials and Methods part. “Our enrolments were only female aged ≥ 20 years because of the NHANES 2001-2002 study design regarding HE4 levels.” (Page 2, line 75-76)
Author Response File: 
Author Response.docx
Reviewer 2 Report
The study by Gallardo et al. addresses an important topic. Despite being well-presented, I have some comments that need to be addressed.
- Did you check the normality of the distribution and residuals to select the appropriate test? Please describe this stage. Without this information, we do not know if the tests were correctly selected.
- Below the tables, there are no extensions of the abbreviations used, e.g. HDL, BMI, AST.
- An extremely important piece of information for readers interested in MetS would be a table (n,%) how many patients in the study group met each MetS criteria.
- Please provide correct formatting as required by the journal (square brackets next to the cited literature, properly formatted bibliography).
Author Response
Point 1: Did you check the normality of the distribution and residuals to select the appropriate test? Please describe this stage. Without this information, we do not know if the tests were correctly selected.
Response 1: Thank you for your constructive critique. We have checked our datasets (HE4 levels) and HE4 levels do not follow the normal distribution. Thus, we have performed log transformation for HE4 levels and HE4 levels followed a log-normal distribution. We have revised the manuscript as below into our Method part. “Demographic characteristics were compared using the ANOVA tests for normally distributed continuous variables, Kruskal-Wallis test for continuous variables without normally distributed, and the Chi-square test for discrete variables. Since HE4 levels was not normally distributed, a logarithmic transformation was performed to normalize the distributions of HE4 levels. The association of HE4 levels with presence of MetS and its components were assessed via multivariate analyses.” (Page 3, line 100-106)
In addition, we also have revised the coefficients values and confidence intervals in table 2 and table 3 because of a logarithmic transformation was performed for HE4. However, the significances of coefficients of the presence and number of metabolic syndrome components for HE4 levels were not changed after log transformation for HE4 levels in revised table 2. Moreover, the significances of coefficients of each metabolic syndrome component for HE4 levels were also not changed in revised table 3. Briefly, the conclusion of our manuscript doesn't need to be changed.
Point 2: Below the tables, there are no extensions of the abbreviations used, e.g. HDL, BMI, AST.
Response 2: Thank you for your constructive critique. We have added the definition of abbreviations below our tables- for example, definition of abbreviations: HDL-C = high-density lipoprotien cholesterol, BMI = body mass index, AST = Aspartate transaminase, and HE4 = human epididymal protein 4.
Point 3: An extremely important piece of information for readers interested in MetS would be a table (n, %) how many patients in the study group met each MetS criteria.
Response 3: Thank you for your constructive critique. We have revised the manuscript as your suggestion into the Results part. “A total of 593 subjects met the MetS criteria, while there were 1511 individuals without MetS. In addition, there were 641 (30.5%), 1349 (64.1%), 721 (34.3%), 651 (30.9%), and 363 (17.3%) patients met each ATP-III defined MetS criteria: high blood pressure, abdominal obesity, low HDL cholesterol, high triglycerides, and hyperglycemia, respectively.” (Page 3, line 118-122)
Point 4: Please provide correct formatting as required by the journal (square brackets next to the cited literature, properly formatted bibliography).
Response 4: Thank you for your constructive critique. We have revised the manuscript as your suggestion, e.g. square brackets next to the cited literature and properly formatted bibliography.
Author Response File: Author Response.docx
