Review for 10.1186/s12876-020-01531-5 (2020)

Reviewer’s report
Title: 
HER2 gene assessment in liquid biopsy of gastric and esophagogastric
junction cancer patients qualified for surgery
Version: 
1 
Date: 
11 Sep 2020
Reviewer's report:
My comments to Authors:
The authors found that HER2 gene copy numbers using a liquid biopsy from
GC/GEJC patients were higher than those from healthy donors. They found that
patients with high HER2 genes in liquid biopsy significantly often showed a high
number of HER2 gene copies in tumor samples, but there was no significant
correlation.
Major Comments:
Methods: 
1. Please explain how the authors determine the region of Interest of the
formalin-fixed paraffin-embedded tumor sample to evaluate HER2 gene or
HER2 protein in Methods.
2. I was wonder how many surgical resection specimen blocks did the authors
analyze? Multi-block analysis can increase sensitivity and accuracy. Please
provide the detail of HER2 evaluation in the tumors in Methods.
Results:
1. Please provide specific median levels in Figure 1 because it seems that there
was no difference between GC patients and healthy donors in HER2 CNV and
serum.
Discussion. 
1. This study included tissue samples taken before the operation without
neoadjuvant treatment and those from patients after treatment. I was wondering
if presurvey intervention can affect these results. Have you checked if there were
differences between both groups? Please comment or discuss it.
2. There are more reports of HER2 expression in liquid biopsy among patients
with breast cancer than gastric cancer. Please discuss or introduce the situation of
HER2 in liquid biopsy in patients with gastric cancer compared with breast
cancer.
3. Did the authors evaluate the relationship between neoadjuvant chemotherapy
response or prognosis and HER2 expression in the liquid biopsy? 
4. The authors should clarify the importance of measuring the HER2 gene in
liquid biopsy before an operation. Because there was no data for GC patients
who used trastuzumab, and there was no significant correlation between HER2
gene copies in liquid biopsy and HER2 amplification in tumor tissue.
5. The authors found that patients with high HER2 genes in liquid biopsy
significantly often showed a high number of HER2 gene copies in tumor
samples, but there was no significant correlation. Was this due to small 
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
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from apparent manipulation?
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