Review for 10.1186/1471-230X-14-74 (2014)

Reviewer's report
Title:Serum trefoil factor 3 as a promising non-invasive biomarker for gastric
cancer screening: A monocentric cohort study in China
Version:10Date:5 January 2014
Reviewer: Mohammad Derakhshan
Reviewer's report:
It is a long-life desire to use non-invasive biomarker to screen high-risk
population for gastric cancer, as the conventional diagnostic tools could not meet
the criteria of screening test. Serum biomarker, especially serum PGI, and PGI/I
have been used in many studies with promising and of course some limitations
across the world, particularly in Japanese population. Recently two groups used
Serum TFF3 as a novel biomarker for gastric cancer and showed some degrees
of superiorities over other screening tests.
In the line of previous publications, the present study put a great effort to confirm
and validate usefulness of serum TFFs in screening of gastric cancer and tried to
elucidate the mechanism of cancer detection by recruitment of a group of
patients with atrophic gastritis as a pre neoplastic stage. The study has gained a
lot from defining clear questions and logical design.
In spite of above, advantages, similar to most studies in this field, a number of
limitations and perhaps ignorance have downgraded the results and put the
reader in partial confidence about conclusion. Here I have listed a number of
issues to improve the quality of results and interpretation of outcomes:
Major issues:
1. Methods: The definitions of non-cancer groups are vague or completely
missing. It is very critical to show readers how you have defined subjects with
atrophic gastritis, non-atrophic gastritis and healthy people (may be volunteers).
Histological definition of atrophic gastritis using “Updated Sydney classification of
gastritis” or newer systems are gold standard, although the problem of inter and
intra-observer agreements has not been solved yet.
2. What was the result of histological subtypes of gastric cancer based on Lauren
classification? It is very important to know what proportion of adenocarcinoma
are of intestinal or diffuse type, as they have direct impact on the association
between background gastric mucosal states and gastric cancer development.
Reporting gastric cancer type as differentiated versus undifferentiated is neither
helpful nor addresses aetiological pathways.
Minor issues:
3. Considering a relatively small sample size, particularly for non-cancer groups,
it is reasonable to assume most of the measured variables have non-normal
distribution unless otherwise proved by normality tests. As authors have used t
tests in statistical analyses, please make clear if the distribution pattern has been
checked first.
4. Results: Please make clear what you mean by average, is it mean, median, or
mode? This problem can be seen in the values with ±sign, perhaps they are SDs,
but again, they can be interquartile, depends on the type of average.
5. Results and Table 1: Results of H.pylori serology in different groups are similar
statistically, which does not make sense. In addition, in CNAG only 52% of
subject are H.pylori positive, that mean 48% of them do not have any evidence of
H.pylori infection, what is the reason for inflammation in such a large group of
subjects. This rate of inflammation cannot be explained by NSIAD usage
particularly in such young age. This concerned me about the accuracy of
measurements.
6. Issue that is more important is the result of serum pepsinogens. Why serum
PGI values are very similar in all four groups and relatively larger than reported
values from other studies on gastric cancer and atrophic gastritis? In other side,
increased PGII in gastric cancer group while PGI is lower than expected is
confusing, it reminds me diffuse type gastric cancer. I suggest you to review
carefully the data presented in the large cohort study (Int J Cancer, 2008; 123:
917). There are two possible explanations for this unusual pattern of PG tests in
your study. First, a systematic error on the measurements, second, a higher
proportion of diffuse type versus intestinal gastric cancer. Therefore, I
recommend to review the histological type of cancers first because it is more
feasible than re-measurement of serum PGs.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests'