An Overview of CD133 as a Functional Unit of Prognosis and Treatment Resistance in Glioblastoma

Round 1

Reviewer 1 Report

CD133 (prominin-1) is a membrane-bound glycoprotein on the surface of cancer stem cells (CSCs) that has been associated with poor prognosis, therapy resistance, and tumor recurrence in high grade gliomas.  This review aims to compile and analyze the current research regarding CD133 as a functional unit in high grade gliomas, exploring its connections to prognosis, the tumor microenvironment, tumor resistance, and tumor recurrence.   Nevertheless, the role of CD133 regarding the prognosis of patients with gliomas is not well defined.  It is suggested that more information regarding the importance of CD133 in gliomas may be of significance in the management of patients with gliomas, although this is speculative. 

1. The main question addressed by this paper is the role of CD133 regarding the prognosis and management of patients with high grade gliomas. 
2. There are many genes which have been suggested to be important for the development of high-grade gliomas, and CD133 is another potential candidate which like the others is not specific enough to be reliable for prognostic issues.  Unfortunately, these patients do poorly in general, and it is hard to find any particular gene that might be useful for either prognostic value or as a treatment option.   
3. The CD133 gene may have some role in understanding the prognosis for patients with these tumors, although like other candidate genes the results are not particularly reliable or specific for these tumors. 
4. This gene like others associated with these tumors is not specific enough to have a critical role in the development of the disease.  I am not sure how an improvement in the methodology would address this issue.  Animal models may be useful in better understanding the role of this gene in the prognosis and treatment of these tumors. 
5. The question arises as to how more information regarding this gene in the pathogenesis of these tumors would be helpful, but everything is speculative at this point.  One would like to hope that a better understanding of the role of this gene in the development of these tumors would be helpful, but unfortunately patients with these tumors do poorly in general and it is hard to change the clinical outcome upon manipulation of any particular gene.   
6. The references are appropriate. 
7. The tables and figures are reasonable.

Minor corrections would be reasonable.

Author Response

Please see the attachment. 

Author Response File: Author Response.docx

Reviewer 2 Report

In this review, the functions of CD 133 in terms of glioblastoma prognosis, role in the microenvironment, resistance to therapy, and disease recurrence are comprehensively presented.

Figures 2 and 3 are not easy to read. Whether the Ingenuity Pathway Analysis(IPA) graphic contributes to understanding is questionable. Perhaps IPA could be better described in the text

Author Response

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Author Response File: Author Response.docx

Reviewer 3 Report

To the authors

The manuscript is a review regarding CD133 in gliomas. CD133 is found on the cell membrane surface of cancer stem cells, including glioblastomas, which expression correlates to poor prognosis, drug resistance, and recurrence. Most recent literature has explored the potential role of CD133 contributing toward glioblastoma steadfastness and reluctance to respond to standard-of-care therapy. Thus, the review deciphers and assimilates most findings (> 2014) on CD133 regarding prognosis, tumor microenvironment, recurrence, and therapy resistance. The review is valuable because several research findings are compiled in one article, which is convenient for readers to stay informed and bridges knowledge over the last nine years. 

For minor revisions, the review should give more information on the CD133 promin gene, with more detail of the five promoters with a diagram. The text of the figures should be enlarged for easier viewing.

The conclusions are consistent with the reviewed papers regarding filling gaps in CD133 downstream signal regulation that may contribute to the patient’s prognosis with appropriate references.

Author Response

Please see the attachment.

Author Response File: Author Response.docx