Review for 10.1186/s12876-025-03932-w (2025)

Title: Serum Cholinesterase Combined with Platelet-to-Hemoglobin Ratio for Predicting
Survival Prognosis in Stage I-III Colorectal Cancer Patients Undergoing Radical Surgery: A
Retrospective Cohort Study
Version: 2 Date: 16 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the cohort size is reasonable, the study is based on a single institution (Harbin
Medical University Cancer Hospital). This may limit the generalizability of the results to other
populations or settings. A multicenter study would be ideal for validating the findings across
diverse patient groups and healthcare environments.
-While the study develops a nomogram for prognosis prediction, there is no mention of external
validation. External validation of the nomogram using a different cohort of patients would
strengthen the applicability and clinical utility of the predictive model.
-The study does not mention whether other potential confounding factors (e.g., comorbidities,
lifestyle factors, or prior treatments) were considered in the analysis. Although the inclusion
criteria are well-defined, further clarifying how confounders were controlled in the statistical
model would be beneficial. For example, were patients with different comorbidities stratified,
or were adjustments made for factors like chemotherapy or radiotherapy?
-The abstract mentions ROC analysis to determine the optimal cut-off points for continuous
variables, but further details are required. Specifically, how were the ROC curves used to
select cut-offs for CHE and PHR? Was this based on the highest Youden index or another
criterion? Providing a brief explanation of this process would strengthen the transparency of the
methodology.
-While the cohort is described in terms of inclusion/exclusion criteria and demographic
characteristics, further details on baseline clinical characteristics (e.g., disease stage distribution,
and histological subtypes) could help contextualize the findings. For example, were there any
significant differences in prognostic outcomes between different CRC stages, or was the focus
entirely on the overall cohort?
-The authors acknowledge that the study’s single-center design limits its external validity. While
this is a common limitation in many studies, the authors must highlight the need for multicenter
validation to strengthen the generalizability of their findings. Conducting prospective studies
across different populations would provide more robust evidence for the applicability of CHE-
PHR as a prognostic marker in CRC.
-Although the study mentions that the CHE-PHR combination was found to be significant across
all CRC stages (I-III), there is little mention of whether there are variations in its prognostic
value across different stages. For example, are these markers more predictive in earlier-stage or
later-stage CRC patients? It might be worth exploring this aspect in more detail, as it could lead
to more tailored, stage-specific approaches to patient care.
-Although the authors acknowledge the limitations of their retrospective study, they do not
address how potential confounding factors, such as comorbidities or preoperative treatments,
might influence the results. Further elaboration on how these factors were controlled or adjusted
for in the analysis would strengthen the reliability of the findings.