Review for 10.1186/s12876-021-01918-y (2021)

Title: Elevated tumor expression of Astroprincin (FAM171A1) is an independent marker of
poor prognosis in colon cancer
Version: 2 Date: 29 May 2021
Reviewer's report:
Kaprio et al. present an investigation of APCN in colon cancer as a potential biomarker. In
several previous publication the authors have created a framework and defined activities of
APCN and this is the first foray into a clinical activity in colon cancer. A large patient cohort
across an extended time span is used to investigate clinical outcome relative to APCN staining
intensity. The outcome is a convincing separation with the highest expression of APCN having
the worst outcome.
Although this manuscript presents some convincing data, a few areas could be improved to
strengthen the overall manuscript. Broadly this includes a bit more discussion and focus on
current biomarkers in colon cancer and the potential usefulness of APCN, presentation of a bit
of additional data, and improvement of grammar and a few areas of clarification. Details of these
comments are below:
1. Nearly half of the background is devoted to discussion of the authors’ recently published work
on APCN (Rasila et al 2019). While this work is clearly pertinent, it could be a bit more succinct.
This would allow instead more discussion of what the current colon cancer biomarkers are and
perhaps why they fall short of being effective. This would then put into perspective the need
for additional biomarkers and the potential importance of the authors works on APCN in colon
cancer. Currently the extent of discussion on other biomarkers in the background is limited to
the following sentence (which does not have a citation): “Several molecular biomarkers have
been suggested as additional prognostic tools to identify those who probably will benefit from
adjuvant treatment after surgery”.
2. An ‘original magnification’ is given for figure 1 in the legend, but the images do not include
a scale bar.
3. Since multiple sections were taken for each patient, how much variability/heterogeneity was
there? Or were scores in these different sections consistent?
4. No strong explanation or rational is given for the test and validation series. It does not sound
like they were treated differently. Some further clarification on this would be helpful.
5. What was the breakdown of stage in the test and validation series? This can be partially
inferred for the test series from Table 2, but it would be useful to include this in the methods (or
perhaps a table) along with some of the other pertinent characteristics of the datasets (gender,
differentiation, side, etc.). All that is listed in the methods under ‘study population’ is age and
survival.
6. In the background section the authors mention challenges in determining which stage II
patients would benefit from adjuvant therapy prior to surgery. Is this something that was
considered or investigated relative to APCN? Do the authors have the data to consider if APCN
expression is useful for specifically stage II and are there any correlations with +/- adjuvant
therapy and outcome?
7. There are several grammatical issues throughout the manuscript. This includes in the abstract –
for example: “marker of poor prognosis independently stage, grade, patient’s age or gender” and
“could potentially select patient for more intense”. There are some instances of run-on sentences
or missing commas and periods. In other places some sentences are a bit short and choppy. In the
methods “slided” is used instead of “slides”. The intended meanings are clear, but corrections
would improve the readability and general flow of the manuscript.