We read with great interest the article by Hu et al1, “Unveiling metabolic pathway dysregulation in the malignant transformation of polyps to colorectal cancer: A single-cell analysis of epithelial cell trajectories.” The study provides novel insights into the metabolic reprogramming underlying colorectal cancer (CRC) initiation, emphasizing the pivotal role of epithelial subpopulations and lactylation-associated pathways. From a surgical perspective, we believe these findings have critical implications for clinical practice, particularly regarding the early identification and targeted intervention of precancerous lesions. The elucidation of fatty acid and bile acid metabolism dysregulation along the malignant trajectory offers potential metabolic biomarkers for risk stratification of polyps. Intraoperative or perioperative metabolic profiling could become a valuable adjunct in distinguishing high-risk adenomas from indolent ones, thereby refining surgical indications and improving patient selection. Moreover, identifying dynamically altered transcription factors (RUNX1, SOX4, STAT3, FOXO1) suggests that metabolic-transcriptional cross-talk may influence tumor invasiveness and recurrence, a concern of paramount importance in gastrointestinal surgery. Lactylation-related regulatory networks proposed by the authors also raise the possibility of intra-tumoral heterogeneity influencing postoperative outcomes. Understanding how metabolic modulation affects surgical stress response and tumor microenvironment adaptation could help design perioperative interventions that minimize recurrence risk. For example, integrating metabolic imaging or lactate-based intraoperative assessment might guide the extent of resection or anastomotic strategy in CRC surgery. In conclusion, Hu et al have provided a valuable molecular framework linking metabolic dysregulation with malignant transformation in CRC. We encourage future translational studies to explore how these single-cell-based metabolic insights can be incorporated into surgical decision-making, postoperative management, and early recurrence surveillance. Such integration would bridge molecular oncology and clinical surgery, ultimately improving patient outcomes. This submission complies with the TITAN Guidelines 2025 governing the declaration and use of AI in scientific writing2. This work complies with the TITAN Guidelines 2025. We appreciate your consideration of our submission and look forward to your feedback. Ethical approval Not applicable. This article is a commentary and does not involve human participants, animal subjects, or patient data requiring ethical approval. Consent Not applicable. No patient-identifiable information is included in this commentary. Sources of funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author contributions Changyou Wang: Conceptualization, literature review, manuscript drafting, critical revision, and final approval of the submitted version. Research registration unique identifying number (UIN) Not applicable. This work is a commentary and does not require registration in a research registry. Guarantor Dr. Changyou Wang. Provenance and peer review Not commissioned.
Zhao et al. (Thu,) studied this question.