Review for 10.1186/s12876-025-03960-6 (2025)

Title: Association of clinicopathological factor with Lymph Node Metastasis in Rectal Cancer
Patients: a retrospective cohort study
Version: 1 Date: 17 Mar 2025
Reviewer:  Qichen Dai
Reviewer's report:
This study aligns with recent research directions exploring the role of inflammatory responses
in cancer progression. By focusing on the critical clinical challenge of predicting lymph
node metastasis (LNM) in rectal cancer, the work holds potential clinical relevance. Non-
invasive hematological markers, if validated as predictive tools, could provide clinicians with
valuable insights. While the study contributes preliminary evidence, the sub-optimal predictive
performance raises concerns about its immediate clinical applicability.
Reviewer Comments:
(1) The authors noted that NLR and PLR demonstrated poor predictive performance (ROC
analysis) when analyzed as continuous variables, yet significant results emerged when
dichotomized into "H-PLR" and "L-PLR" groups using arbitrary cutoffs. The rationale for
selecting these specific cutoff values (e.g., median, algorithm-derived thresholds) remains
unclear. Categorizing continuous variables without robust justification risks introducing
statistical bias, thereby undermining the validity of conclusions. Please clarify the methodology
for cutoff determination.
(2) Sensitivity analyses evaluating the impact of alternative cutoff thresholds on predictive
performance are absent. The authors should supplement their analysis with a sensitivity
assessment using multiple cutoffs to verify the result stability.
(3) No comparative data on clinicopathological characteristics between the dichotomized groups
(e.g., H-PLR vs. L-PLR) are provided. Unaccounted imbalances in baseline variables may
confound outcomes. Propensity score matching is strongly recommended to mitigate this risk.
(4) The binary classification of LNM status (present/absent) oversimplifies prognostic
stratification. Given that rectal cancer N-staging directly depends on metastatic lymph node
count, re-evaluating NLR/PLR against quantitative nodal burden (N0/N1/N2) may yield more
clinically meaningful insights.
(5) Key clinicopathological factors influencing LNM—including elevated CEA, dMMR/MSI-
H status, EGFR/VEGFR expression, and KRAS/BRAF/p53 mutations—are not addressed.
Omitting these confounders weakens the model’s clinical relevance.
(6) Statistical notation in tables requires standardization: Interquartile ranges (IQRs) should
replace ranges when reporting medians (e.g., "median, IQR]" instead of "median, range").
(7) The core hypothesis—that NLR/PLR predict LNM—is inadequately supported by the
low AUC values (NLR 0.512; PLR 0.548). These markers may lack specificity for systemic
inflammation. Expanding the analysis to include other indices (e.g., SII, MLR, CRP, AGR) is
advised.
(8) Language note: The phrase "Compared with other comparable studies..." contains redundant
phrasing. Revise to "Compared with previous studies..." for clarity.
(9) The retrospective, single-center design introduces selection bias and limits generalizability.
Future validation through multicenter prospective studies is essential to enhance external
validity.
The study addressed a clinically significant question with notable translational potential. Given
the methodological limitations outlined in the review, I recommend Major Revision to address
the statistical concerns (e.g., cutoff justification, sensitivity analyses), incorporate key clinical
confounders, and refine the outcome classification.