Review for 10.1186/s12876-025-04153-x (2025)

Title: Overexpression of Protein Kinase C iota as a Prognostic Marker and Its Role in Oxaliplatin
Resistance in colorectal Cancer
Version: 3 Date: 22 May 2025
Reviewer's report:
The manuscript titled "Protein Kinase C Iota (PKC#) Overexpression Predicts Poor Prognosis
and Chemotherapy Resistance in Colorectal Cancer" presents a clinically meaningful and
well-structured study. The correlation between PKC# expression and oxaliplatin resistance is
novel and potentially impactful for prognostic stratification in colorectal cancer (CRC). While
the study is well-executed, a few clarifications and refinements are recommended: 1. Clarify
multivariate analysis interpretation. While PKC# expression is significantly associated with
OS and PFS in Kaplan-Meier analysis, it does not retain significance in the multivariate Cox
model. The authors are encouraged to further discuss the potential reasons for this inconsistency
(e.g., sample size limitations, variable interactions) and clarify whether PKC# remains clinically
meaningful despite statistical insignificance in the multivariate context. 2. To enhance the
scientific rigor and contextual relevance of the manuscript, the authors are encouraged to
incorporate several recent studies related to colorectal cancer prognosis and chemotherapy
resistance. BEAN1 has been shown to correlate with poor prognosis and oxaliplatin resistance
in rectal adenocarcinoma (PMID: 39276259), supporting the discussion of PKC#’s role
in chemoresistance. Immune-related prognostic markers such as pan-immune-inflammatory
values (PMID: 40046636) and combined NP/LHb indices with monocyte count (PMID:
40087531) offer additional evidence for the clinical significance of systemic inflammation
in colorectal cancer, which aligns with the manuscript’s findings. Furthermore, metabolic
indicators including serum calcium (PMID: 40162418) have demonstrated prognostic value and
can complement the discussion of body weight and lipid profiles in predicting progression-free
survival. Finally, research on nutritional and inflammatory markers for anastomotic leakage
(PMID: 40291866) can be cited in the Introduction to highlight the complexity of CRC
management and the importance of comprehensive prognostic evaluation. Incorporating these
references will improve the manuscript’s depth, strengthen its discussion, and situate the
findings within the broader landscape of colorectal cancer research. 3. Improve figure and table
labeling. Figures 2–5 and Table 1–2 are informative, but some axis labels, legends, and subfigure
annotations (e.g., "Figure 2a–d") are not clearly labeled or described in the figure legends.
Please revise for clarity and consistency to ensure figures are self-explanatory to readers. 4.
Language and grammar polishing. Although the manuscript is generally well-written, there
are instances of awkward phrasing and grammatical errors (e.g., "tumor burden did not show
significant correlations with PKC# expression" could be reworded for clarity). A professional
English editing service or a native speaker review is recommended to improve fluency and
readability. 5. Add discussion on potential clinical applications. The conclusion mentions PKC#
as a therapeutic target, but the discussion could be expanded with references to current progress
or limitations of PKC#-targeted therapies (e.g., aurothiomalate or other inhibitors in clinical
trials). This would help contextualize the translational potential of the findings.