LMP1-EBV Gene Deletion Mutations and HLA Genotypes of Nasopharyngeal Cancer Patients in Vietnam

Round 1

Reviewer 1 Report (Previous Reviewer 1)

The manuscript need to be revised. The grammar and sentence structure must be improved. An English editor is strongly recommended. The findings outlined manuscript needs to be reorganized so that the topics are discussed as a unit. This means that the overall manuscript and sentence structure be more synthetic (short and to the point) 

The Material and Methods section. The section 2.3 study equipment is not needed. One should only indicate specialized reagents/equipment in the appropriate methods sections and as a special section that included  common lab items.

Please correctly use of  paraffin blocks and not paraffin candles.

 

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 2 Report (New Reviewer)

The manuscript entitled "LMP1-EBV gene deletion mutations and HLA genotypes of nasopharyngeal cancer patients in Vietnam" by Trinh et al. describes a study of 108 nasopharyngeal biopsy tissue samples of patients with nasopharyngeal carcinoma (NPC) in Vietnam, of whom a majority have LMP1-EBV gene 30bp deletions. Some HLA alleles appear to be associated with the occurrence of NPC. The authors assume that most of the EBV-associated NPC in Viet Nam harbor the deleted variant of LMP1, which is in line with other studies from South East Asia. The study results are of interest for the field. However, I believe this manuscript is not appropriate for publication in its current form.

In the Methods section (2.2 to 2.6) the sample selection procedures, the equipment and the chemicals used are presented in a very detailed manner. It is recommended to noticeably shorten these parts of the manuscript.

The Results sections describes in detail the different HLA types found in the study cohort. At first sight, the HLA alleles detected represent a common distribution which would be expected from people who originate from the Vietnam area. No HLA data of a control group is shown which is necessary for studies about genetical associations. In addition, it is not clear how the statistical analysis was performed. Has the Hardy-Weinberg Equilibrium been checked? Has the Bonferroni Correction been applied to correct for the number of different HLA alleles found in the total study cohort? The authors should generally check the statistics applied for the analyses performed.

 

Minor points:

Page 6, lines 215 -217, and Page 7, lines 225 – 228: Please check the wording of these sentences which is currently not clear.

In general, the Results section should be improved with respect to the English language.

Discussion section, page 11, lines 335 – 343: Current HLA nomenclature rules must be used (DRB1*12:01 instead of DRB1*1201)

In summary, I believe a major revision of the manuscript is recommended.

Author Response

Please see the attachment

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report (New Reviewer)

The manuscript entitled "LMP1-EBV gene deletion mutations and HLA genotypes of nasopharyngeal cancer patients in Vietnam" by Trinh et al. has been revised by the authors and most points were addressed. Regarding the statistics applied the authors claim that their study used a “descriptive analysis design”. For such an approach the lack of a control group and weaknesses in statistics may be acceptable. For an HLA association study the statistics applied is still not sufficient.

The language editing service of the journal should be used to improve the quality of the manuscript.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

The authors studied LMP1 deletions and its association with HLA in NPC patients found in a subset of the Vietnamese population. Given the present controversy on the role of EBV in breast cancer oncogenesis it is confusing the reader why there appears an undue consideration on breast cancer in this discussion. The authors should focus on their data findings as it relates to NPC.

The authors would aid the reader greatly if comparison of the various HLA types in their population and comparison with other studies along with LMP deletion incidence were summarized in a table. This would allow for a more focused discussion. As it is presently written the reader quickly becomes overwhelmed with the data sets and looses the final message. A listing of the HLA types in the general population as a basis of comparison should also be included.

The manuscript would be vastly improved by editing as many of the sentences were grammatically cumbersome and could be made more concise. The methods section could be better consolidated. It is strongly recommended that the authors use an English editor and shorten the paper.

Reviewer 2 Report

 

In this MS, Trinh et al describes LMP1 mutations in NPC biopsies from Vietnam and correlates it with different HLA types. The main finding is that HLA-B15 and the 30 bp deletion in EBV LMP1 are significantly correlated. The data are interesting but the paper is dismally poorly written.  It was quite a challenge to go through it.  

 

Specific comments:

 

1: References in line 49 are all wrong.  The correct reference for non-immnuogenicity of NPC LMP1 is  Trivedi et al, Eur J Cancer 1994;30A(1):84-8. doi: 10.1016/s0959-8049(05)80024-3.

and for increased tumorigenicity of NPC LMP1, the correct reference is Hu et al, Hu LF, et al. Oncogene. 1993. PMID: 8389032

 

2: Lines 52 to 58 are pretty messed up and must be written in better and more understandable English.

 

3: Line 59-63, again, English is very poor. These objectives are ok but the verb is missing. What do you want to do with them? Study? Analyze? Investigate?

 

4: Material and methods: Here as well, English is very poor. …….. It should be rewritten:… of which 38 were fresh tissue samples and 70 were candle parafinned samples. As control, 30 PBL samples from NPC patients were also included.

 

5: Equipments and tools? Really? Never seen that ever before in a manuscript.

 

6: Line 205: Embedded in paraffin candles? Some serious rewriting is needed here.

 

Minor:

1: Correct typo PNC to NPC in line 38, 43, 50 and throughout the MS.

2: … line 42… one of the EBV genes found….. Instead of found, a more correct word would be expressed

3: Line 60 Arch biopsy? I presume it is archived and that’s how it should be referred to.