PONE-D-20-17649

Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression

PLOS ONE

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: RNA-binding protein Musashi-2 (MSI2) controls the translation of proteins that support stem cell identity and lineage determination and is associated with progression in some cancers. The present study explore the prognostic significance of MSI2 in CRC polyps and colon cancer. Its well-planned study that explicitly signifies the role of MSI2 in CRC. However, the data on its role in initiation is still unclear. In order to clarify its role and prognostic significance, it will be interesting to see MSI2 expression alteration in hyperplastic, and serrated polyp types. How microsatellite instability impact MSI2 expression and does its differential expression is associated with mutational status of tumor.

Minor Suggestion: A high level of MSI2 expression in the metastasis was also associated with lymph node positivity (median values with quartiles 270 [250;280] for N0 versus 265 [242;280] for N1 versus 280 [275;290] for N2; average values, 268 versus 262 versus 281; p=0.04), and with higher differentiation grade of the primary tumor (p = 0.000). Clearly mention the p-value observed for the study.

Reviewer #2: The manuscript entitled "Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression" by Leonid Kharin et al. Here authors, addressed the critical role of Musashi-2 (MSI2) in colorectal cancer and metastasis. The idea of this article is exciting. The author showed a stage-wise increase in the expression of MSI2. Also, it showed the critical role of MSI cell proliferation and growth. However, colon cancer-promoting role of MSI2 is already reported. The techniques or methodology used is up to date. However, the following points need to be addressed.

1. In one section of the results, the author stated that the expression of MSI2 in primary tumors did not correlate with CDH1 expression. However, in another section using the TCGA data set, the author showed a positive correlation between MSI2 protein expression and CDH1 protein. This ambiguity needs to be addressed.

2. The whole idea of this manuscript to show the significance of MSI2 in prognosis colon cancer progression. It would be better to use regression and ROC analysis methods to show the prognostic significance of MSI2 in predicting disease progression.

3. Figure1A: MSI2 expression (representative IHC images) in adenocarcinoma and liver metastasis is not clear and hard to interpret. Higher magnification insert would help in compression between them.

4. Figure1D: Author showed MSI2 expression comparison between grade 3 with grade1 & 2. It would be better to show compressions among normal and all the grades with representative IHC images of MSI2.

5. Figure4G-H: typo error in Y axis, % colony formation instead of % cell viability.

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Reviewer #1: No

Reviewer #2: No

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Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression

PONE-D-20-17649R1

Dear Dr. Kharin,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Punita Dhawan

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The manuscript entitled "Prognostic role and biologic features of Musashi-2 expression in colon polyps and during colorectal cancer progression" is now looks satisfactory and ready for acceptance.

Reviewer #3: Authors have made revisions that are sufficient to address the concerns. Thanks for all the revisions.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No