Malondialdehyde, an Oxidative Stress Marker in Oral Squamous Cell Carcinoma—A Systematic Review and Meta-Analysis

Comments

Reply

"The authors provide a meta-analytic review that suggests that serum and
plasma MDA, a by-product of oxidative stress and lipid peroxidation, may serve as a useful biomarker for oral cancer. While they attempt to support that MDA may serve as a potential prognostic marker for OSCC, only a few studies discussed support the notion and their data provided in the manuscript do not directly support the concept. There is, however, a clear indication that MDA is higher in serum and plasma in patients with OSCC compared to controls in the studies evaluated. The finding that this is opposed by tissue levels of MDA is intriguing despite having only a few studies in which these measurements were taken.

We have modified the prognostic marker to diagnostic marker in accordance with comment.

It is worth noting that the Tables [2-4] are cumbersome to read and do not have legends describing the shorthand [i.e., for the sample site], Table 1 really should be Supplementary, and the Figures are of very poor quality - this all should be addressed regardless of the Reviewers' critiques and if they do not comment on this then I will still recommend revision to address these shortcomings.

Footnotes for abbreviations provided under Tables 2-4. Figures modified.

However, overall this manuscript may be impactful in supporting preclinical and clinical investigations of the role of oxidative stress in OSCC and the potential utility of MDA as an indicator of disease progression and severity."

Thank you for the positive comment.

Major Comments

Reply

Line 169; 177; Figure 1 and others, the usage of terms ‘qualitative synthesis’ and ‘quantitative synthesis’ for selecting studies for further analysis in cohort studies are scientifically incorrect and should be corrected.

Terminologies changed as Systematic Review and Meta-Analysis.

Table 1 and line 167: discusses 46 studies were included whereas Figure 1 mentions 45, this should be corrected.

Mistake corrected in Fig 1.

Table 2, 3 and 4; Figures 2,3,4 and 5 provide the full forms of the abbreviations as footnotes

The full form of abbreviations are provided as footnotes.

Figure 2,3,4,5 better resolution of the images is required to read through them.

Fig. 2/3/4/5 have been modified.

The expression unit of MDA varies in different studies, such as Subapryia et. al 2002 measures in nmol/100mg protein whereas Gokul et. al. 2010 measures in nmol/mg of ‘Ti’, OR, as in Subapryia et. al 2002 measures ‘Pl’ level as nmol/l and Rasool et. al. 2004 measures in µmol/ml.  Were variation of units such as these was considered while analysis? this should be explained in the method section.

2.9 Methodological Section – Statistical Analysis, Page 4, Lines 182 – 183. Only similar unites have been included in the meta-analysis.

It will be easier for the readers if the authors include a column or mark as an asterisk in table 2 mentioning which of these studies were used for further quantitative analysis

Asterisk marks have been added in the Table 2 to indicate the studies used for quantitative analysis.

There is no mention, interpretation, or discussion of the Table 2/3/4 in the results section as text.

In accordance with the comments Tables 1/2/3/4 are mentioned in the Results, Lines 196 – 199 of page 4

The authors should also comment and interpret the I-square value of the forest plots, as Figure 2,3 & 4 has I-square values of 100%, 93% and 100% respectively. It is generally accepted that >50% of this value in a meta-analysis is an indication of serious heterogeneity and hence data inconsistency. This is also reflected in the plots as the mean differences are mostly borderline to the line of null effect. This needs to be explained.

The mentioned comment is addressed in the Result section, Lines 211 – 213 of Page 4.

A very interesting systematic review with metanalysis about the role of malondialdehyde in oral squamous cell carcinoma. I found the article very informative, complete, and easy to read. I think it will be eligible to be published after some revisions:

Thank you for your positive comment.

In 2.7. Retrieval of Full-text articles and Evaluation you should specify exactly the authors that performed screening and discussed, according to each procedure (capital initials will be enough).

In page number 3, Methodology 2.7, Authors Initials have been provided concerning their roles and contributions.

It seems there is too much difference among articles screened in the various databases (it seems strange that in Scopus you retrieved 140 articles, while in WOS just 7...please check)

Re checked. Though Scopus showed 140 similar articles, only 18 articles were completely relevant to this study and WOS showed 7 relevant articles.

Page 2 line 52 you should add: "Although various treatments have been proposed to manage this type of cancer, its aggressiveness and ability to metastasize makes this cancer one of the most difficult to treat, so early diagnosis is crucial when facing this condition." and cite some articles such as: doi: 10.3390/curroncol28040213. and doi: 10.3390/medicina57060563.

Similar comments have been added in Page 14 Lines 370 – 374 with reference cited as 82, 83. Reasons for not citing the mentioned articles in the introduction is that it will alter the reference order already documented in Tables, Figures and Text. 

I would probably modify figure 2...there is no need to have a -20 + 20 fold if higher values are around 7-8 folds in the mean difference....

Mean Difference Range Values in Figure 2 and 3 modified as per the comments.

Comments

Reply

"The authors provide a meta-analytic review that suggests that serum and
plasma MDA, a by-product of oxidative stress and lipid peroxidation, may serve as a useful biomarker for oral cancer. While they attempt to support that MDA may serve as a potential prognostic marker for OSCC, only a few studies discussed support the notion and their data provided in the manuscript do not directly support the concept. There is, however, a clear indication that MDA is higher in serum and plasma in patients with OSCC compared to controls in the studies evaluated. The finding that this is opposed by tissue levels of MDA is intriguing despite having only a few studies in which these measurements were taken.

We have modified the prognostic marker to diagnostic marker in accordance with comment.

It is worth noting that the Tables [2-4] are cumbersome to read and do not have legends describing the shorthand [i.e., for the sample site], Table 1 really should be Supplementary, and the Figures are of very poor quality - this all should be addressed regardless of the Reviewers' critiques and if they do not comment on this then I will still recommend revision to address these shortcomings.

Footnotes for abbreviations provided under Tables 2-4. Figures modified.

However, overall this manuscript may be impactful in supporting preclinical and clinical investigations of the role of oxidative stress in OSCC and the potential utility of MDA as an indicator of disease progression and severity."

Thank you for the positive comment.

Major Comments

Reply

Line 169; 177; Figure 1 and others, the usage of terms ‘qualitative synthesis’ and ‘quantitative synthesis’ for selecting studies for further analysis in cohort studies are scientifically incorrect and should be corrected.

Terminologies changed as Systematic Review and Meta-Analysis.

Table 1 and line 167: discusses 46 studies were included whereas Figure 1 mentions 45, this should be corrected.

Mistake corrected in Fig 1.

Table 2, 3 and 4; Figures 2,3,4 and 5 provide the full forms of the abbreviations as footnotes

The full form of abbreviations are provided as footnotes.

Figure 2,3,4,5 better resolution of the images is required to read through them.

Fig. 2/3/4/5 have been modified.

The expression unit of MDA varies in different studies, such as Subapryia et. al 2002 measures in nmol/100mg protein whereas Gokul et. al. 2010 measures in nmol/mg of ‘Ti’, OR, as in Subapryia et. al 2002 measures ‘Pl’ level as nmol/l and Rasool et. al. 2004 measures in µmol/ml.  Were variation of units such as these was considered while analysis? this should be explained in the method section.

2.9 Methodological Section – Statistical Analysis, Page 4, Lines 182 – 183. Only similar unites have been included in the meta-analysis.

It will be easier for the readers if the authors include a column or mark as an asterisk in table 2 mentioning which of these studies were used for further quantitative analysis

Asterisk marks have been added in the Table 2 to indicate the studies used for quantitative analysis.

There is no mention, interpretation, or discussion of the Table 2/3/4 in the results section as text.

In accordance with the comments Tables 1/2/3/4 are mentioned in the Results, Lines 196 – 199 of page 4

The authors should also comment and interpret the I-square value of the forest plots, as Figure 2,3 & 4 has I-square values of 100%, 93% and 100% respectively. It is generally accepted that >50% of this value in a meta-analysis is an indication of serious heterogeneity and hence data inconsistency. This is also reflected in the plots as the mean differences are mostly borderline to the line of null effect. This needs to be explained.

The mentioned comment is addressed in the Result section, Lines 211 – 213 of Page 4.

A very interesting systematic review with metanalysis about the role of malondialdehyde in oral squamous cell carcinoma. I found the article very informative, complete, and easy to read. I think it will be eligible to be published after some revisions:

Thank you for your positive comment.

In 2.7. Retrieval of Full-text articles and Evaluation you should specify exactly the authors that performed screening and discussed, according to each procedure (capital initials will be enough).

In page number 3, Methodology 2.7, Authors Initials have been provided concerning their roles and contributions.

It seems there is too much difference among articles screened in the various databases (it seems strange that in Scopus you retrieved 140 articles, while in WOS just 7...please check)

Re checked. Though Scopus showed 140 similar articles, only 18 articles were completely relevant to this study and WOS showed 7 relevant articles.

Page 2 line 52 you should add: "Although various treatments have been proposed to manage this type of cancer, its aggressiveness and ability to metastasize makes this cancer one of the most difficult to treat, so early diagnosis is crucial when facing this condition." and cite some articles such as: doi: 10.3390/curroncol28040213. and doi: 10.3390/medicina57060563.

Similar comments have been added in Page 14 Lines 370 – 374 with reference cited as 82, 83. Reasons for not citing the mentioned articles in the introduction is that it will alter the reference order already documented in Tables, Figures and Text. 

I would probably modify figure 2...there is no need to have a -20 + 20 fold if higher values are around 7-8 folds in the mean difference....

Mean Difference Range Values in Figure 2 and 3 modified as per the comments.