Relation of Mean Platelet Volume (MPV) with Cancer: A Systematic Review with a Focus on Disease Outcome on Twelve Types of Cancer

Round 1

Reviewer 1 Report

This manuscript is well-written and also an intact summarization of MPV studies in recent 10 years. I have some suggestions.

1. Figure 1 picture resolution is seemly not enough. 

2. The authors simply explain why MPV change influences survival outcomes or metastatic risk. According to previous research, the authors can try to propose possible underlying mechanisms by which MPV change enhances tumor aggressiveness. Please add objective explanations to the discussion section.

Author Response

This manuscript is well-written and also an intact summarization of MPV studies in recent 10 years. I have some suggestions.

We would like to thank the reviewer for the comments. We provide a point-by-point answer to the raised points.

1. Figure 1 picture resolution is seemly not enough.

The figure analysis has changed.

2. The authors simply explain why MPV change influences survival outcomes or metastatic risk. According to previous research, the authors can try to propose possible underlying mechanisms by which MPV change enhances tumor aggressiveness. Please add objective explanations to the discussion section.

The discussion has been updated as follows:

Regarding the relationship between MPV and tumor aggressiveness, it's important to mention that the increased reactivity of larger platelets is due, among others, to increased expression of integrin αIIbβ3 and glycoprotein (GP) Ibα [1]. αIIbβ3 may participate in platelet–tumor cell interaction in tumor metastasis through the binding of metalloproteinase domain-containing protein 9 (ADAM-9). This interaction could form a physical shield around cancer cells protecting them from natural killer (NK) cell lysis [2]. Also, it has been observed that activated platelets facilitate tumor cell adhesion to endothelial cells through a αIIbβ3-associated mechanism [3]. Moreover, activated platelets can facilitate tumor cell extravasation after the extracellular matrix degradation by matrix metalloproteinase-2 (MMP-2) [4]. Regarding the GPIba, GPIbα-mediated platelet adhesion to angiogenic vessels enhances angiogenesis, and prevents hemorrhage from newly formed vessels contributing to cancer development and aggressiveness [5].

 

1. Sabrkhany, S.; Kuijpers, M.J.E.; oude Egbrink, M.G.A.; Griffioen, A.W. Platelets as Messengers of Early-Stage Cancer. Cancer Metastasis Rev 2021, 40, 563–573, doi:10.1007/s10555-021-09956-4.
2. Lavergne, M.; Janus-Bell, E.; Schaff, M.; Gachet, C.; Mangin, P. Platelet Integrins in Tumor Metastasis: Do They Represent a Therapeutic Target? Cancers 2017, 9, 133, doi:10.3390/cancers9100133.
3. Dardik, R.; Kaufmann, Y.; Savion, N.; Rosenberg, N.; Shenkman, B.; Varon, D. Platelets Mediate Tumor Cell Adhesion to the Subendothelium under Flow Conditions: Involvement of Platelet GPIIb-IIIa and Tumor Cell ?V Integrins. Int. J. Cancer 1997, 70, 201–207, doi:10.1002/(SICI)1097-0215(19970117)70:2<201::AID-IJC11>3.0.CO;2-L.
4. Choi, J.-H.; Kim, H.; Kim, H.-S.; Um, S.H.; Choi, J.-W.; Oh, B.-K. MMP-2 Detective Silicon Nanowire Biosensor Using Enzymatic Cleavage Reaction. Journal of Biomedical Nanotechnology 2013, 9, 732–735, doi:10.1166/jbn.2013.1541.
5. Bendas, G.; Schlesinger, M. The GPIb-IX Complex on Platelets: Insight into Its Novel Physiological Functions Affecting Immune Surveillance, Hepatic Thrombopoietin Generation, Platelet Clearance and Its Relevance for Cancer Development and Metastasis. Exp Hematol Oncol 2022, 11, 19, doi:10.1186/s40164-022-00273-2.

 

Reviewer 2 Report

Detopoulou et al submitted a systemic review discussing the possibility of using mean platelet volume (MPV) in the diagnosis of different types of cancers. The topic is interesting to the readers, and authors have a fair quality of presentation. However, I have some points that might help authors to make the content more scientific and significant. 

 

(1)   Although it is well-known, it still would be better to give a full name of MPV in the abstract when first mentioned. 

(2) In the introduction, it would be great if authors can add more sentences discussing the importance of the study.

(3)   Line 104-105; add the word “comparison”.

(4)   Why did the authors exclude the animal studies (In vivo studies)?

(5)   3.1 gastric cancer: please cite table 2. 

(6)   Line 218; add “in” after found.

(7)   Please cite table 7 in all bladder cancer, gallbladder cancer and MM. 

(8)   Please calculate the number of studies included in the review as they were 83, not 82 as being mentioned.

(9)   Figure 2 in the discussion was very interesting and simple to follow, but why the authors did not include breast cancer?

 

I wish the authors best of luck with their revision.

Author Response

Detopoulou et al submitted a systemic review discussing the possibility of using mean platelet volume (MPV) in the diagnosis of different types of cancers. The topic is interesting to the readers, and authors have a fair quality of presentation. However, I have some points that might help authors to make the content more scientific and significant. 

We would like to thank the reviewer for the comments. We have addressed all the comments.

Although it is well-known, it still would be better to give a full name of MPV in the abstract when first mentioned. 

Done

In the introduction, it would be great if authors can add more sentences discussing the importance of the study.

The introduction was accordingly updated.

Line 104-105; add the word “comparison”.

Done

Why did the authors exclude the animal studies (In vivostudies)?

Although laboratory animals have served in understanding mechanisms of human cancer, there are still many differences in animal and human comparative biology (Rangarajan et al. 2003, DOI: 10.1038/nrc1235). For example, the basal metabolic rate in mice is seven times higher in mice than in humans possibly altering the redox status and thus cancer susceptibility (Ames et al. 1993, DOI: 10.1073/pnas.90.17.7915) and differences in telomere length may apply (Rangarajan et al. 2003, DOI: 10.1038/nrc1235). In addition, cancer therapies tested in animals do not always work in humans, while drug dose, formulas and schedules may still differ (Ledford et al. 2011, DOI: 10.1038/477526a).

In this context, human studies can better reflect the complexity of real-life, especially in cancer, in which each patient constitutes a different ontology by genetic, environmental, pathophysiological and therapeutical means. That is why we believe that the relationship of MPV with cancer should be better considered in a real-life context.

 

3.1 gastric cancer: please cite table 2. 

It is cited.

 Line 218; add “in” after found.

Done

 Please cite table 7 in all bladder cancer, gallbladder cancer and MM. 

Done

Please calculate the number of studies included in the review as they were 83, not 82 as being mentioned.

Thank you for this comment. We have corrected the number.

Figure 2 in the discussion was very interesting and simple to follow, but why the authors did not include breast cancer?

Thank you for this observation. We have accordingly changed the Figure to include breast cancer. 

Reviewer 3 Report

Review for the manuscript “Relation of mean platelet volume (MPV) with cancer: a  systematic review with a focus on disease outcome on 3 twelve types of cancer”.

 The authors wanted to investigate the possible alterations of MPV in various types of cancer. They also, wanted to establish a relation between MPV, disease outcome, effectiveness of treatment and its prognostic value. They searched two databases PubMed and Google Scholar from 2010 to 2022. The authors mentioned inclusion and exclusion criteria. They identified 82 studies including 21,034 participants with 12 different types of cancer.

 The results of this review focused on the role of MPV that could be used as a potential biomarker in cancer diagnosis and could be a useful tool for optimization of treatment strategies.

 The presentation of the results was clear and included 7 tables and two figures.

The results were useful for different cancer diagnosis, tratment and prognosis. 

Author Response

We would like to thank the reviewer for the nice comments.

Round 2

Reviewer 2 Report

All comments have properly been addressed.