Title: Circulating miRNA-202-3p is a potential novel biomarker for diagnosis of type 1 gastric
neuroendocrine neoplasms
Version: 1 Date: 06 Jan 2021
Reviewer:  Roberta Modica
Reviewer's report:
In this paper miRNA-202-3p is a proposed as a potential novel biomarker for type 1 gastric
neuroendocrine neoplasms (g-NENs). The need of reliable diagnostic biomarkers is of utmost
importance in the field of NEN.
This is an interesting study, with a relatively novel concept, which would likely add new insights.
There are however some weaknesses, that should be addressed or revised.
Inclusion criteria are based on 2016 NCCN guidelines, which are updated yearly; authors should
explain this choice. Diagnostic and inclusion criteria have to be clarified, as it is stated that
“to investigate the characteristics of patients in more detail, gastroscopy and pathology were
performed after collecting blood samples” but patients needed a pathological diagnosis of g-
NEN to be enrolled. Furthermore, if the blood sample was taken in all patients, why CgA is not
available in 9 subjects?
Do control participants underwent gastroscopy for other purposes?
If patients were enrolled with pathological diagnosis of g-NEN, in the 5 subjects without polyps
authors should describe the kind of lesion detected or if it was an incidental finding.
Pharmacological treatment with somatostatin analog or other drugs should be specified.
CgA is expressed in pg/l in the text and ng/ml in the tab, please standardize.
It is stated that the serum expression of miRNA-202-3p was quantified to confirm the expression
of miRNA-202-3p in the tumor tissue, but was the tissue expression evaluated in the same
subjects? Consequently, the serum expression was performed before or after tumor removal?
The expression of miRNA in subjects and controls could be easier to understand if expressed
with the same exponent (tab 3).
The dense vascular network and high blood tumor flow are suggested to explain the serum
miRNA elevation, but other hypothesis should be proposed due to the small tumor dimensions
in the majority of patients.
In summary, although interesting, the power of this miRNA as a diagnostic biomarker in g-
NEN is moderate and this limit should be highlighted in the conclusions, as well as the limited
number of samples.
Title: Circulating miRNA-202-3p is a potential novel biomarker for diagnosis of type 1 gastric
neuroendocrine neoplasms
Version: 1 Date: 06 Jan 2021
Reviewer:  Roberta Modica
Reviewer's report:
In this paper miRNA-202-3p is a proposed as a potential novel biomarker for type 1 gastric
neuroendocrine neoplasms (g-NENs). The need of reliable diagnostic biomarkers is of utmost
importance in the field of NEN.
This is an interesting study, with a relatively novel concept, which would likely add new insights.
There are however some weaknesses, that should be addressed or revised.
Inclusion criteria are based on 2016 NCCN guidelines, which are updated yearly; authors should
explain this choice. Diagnostic and inclusion criteria have to be clarified, as it is stated that
“to investigate the characteristics of patients in more detail, gastroscopy and pathology were
performed after collecting blood samples” but patients needed a pathological diagnosis of g-
NEN to be enrolled. Furthermore, if the blood sample was taken in all patients, why CgA is not
available in 9 subjects?
Do control participants underwent gastroscopy for other purposes?
If patients were enrolled with pathological diagnosis of g-NEN, in the 5 subjects without polyps
authors should describe the kind of lesion detected or if it was an incidental finding.
Pharmacological treatment with somatostatin analog or other drugs should be specified.
CgA is expressed in pg/l in the text and ng/ml in the tab, please standardize.
It is stated that the serum expression of miRNA-202-3p was quantified to confirm the expression
of miRNA-202-3p in the tumor tissue, but was the tissue expression evaluated in the same
subjects? Consequently, the serum expression was performed before or after tumor removal?
The expression of miRNA in subjects and controls could be easier to understand if expressed
with the same exponent (tab 3).
The dense vascular network and high blood tumor flow are suggested to explain the serum
miRNA elevation, but other hypothesis should be proposed due to the small tumor dimensions
in the majority of patients.
In summary, although interesting, the power of this miRNA as a diagnostic biomarker in g-
NEN is moderate and this limit should be highlighted in the conclusions, as well as the limited
number of samples.
Please review this paper.
user
Title: Circulating miRNA-202-3p is a potential novel biomarker for diagnosis of type 1 gastric
neuroendocrine neoplasms
Version: 1 Date: 06 Jan 2021
Reviewer:  Roberta Modica
Reviewer's report:
In this paper miRNA-202-3p is a proposed as a potential novel biomarker for type 1 gastric
neuroendocrine neoplasms (g-NENs). The need of reliable diagnostic biomarkers is of utmost
importance in the field of NEN.
This is an interesting study, with a relatively novel concept, which would likely add new insights.
There are however some weaknesses, that should be addressed or revised.
Inclusion criteria are based on 2016 NCCN guidelines, which are updated yearly; authors should
explain this choice. Diagnostic and inclusion criteria have to be clarified, as it is stated that
“to investigate the characteristics of patients in more detail, gastroscopy and pathology were
performed after collecting blood samples” but patients needed a pathological diagnosis of g-
NEN to be enrolled. Furthermore, if the blood sample was taken in all patients, why CgA is not
available in 9 subjects?
Do control participants underwent gastroscopy for other purposes?
If patients were enrolled with pathological diagnosis of g-NEN, in the 5 subjects without polyps
authors should describe the kind of lesion detected or if it was an incidental finding.
Pharmacological treatment with somatostatin analog or other drugs should be specified.
CgA is expressed in pg/l in the text and ng/ml in the tab, please standardize.
It is stated that the serum expression of miRNA-202-3p was quantified to confirm the expression
of miRNA-202-3p in the tumor tissue, but was the tissue expression evaluated in the same
subjects? Consequently, the serum expression was performed before or after tumor removal?
The expression of miRNA in subjects and controls could be easier to understand if expressed
with the same exponent (tab 3).
The dense vascular network and high blood tumor flow are suggested to explain the serum
miRNA elevation, but other hypothesis should be proposed due to the small tumor dimensions
in the majority of patients.
In summary, although interesting, the power of this miRNA as a diagnostic biomarker in g-
NEN is moderate and this limit should be highlighted in the conclusions, as well as the limited
number of samples.
assistant