Revisiting lipid dysregulation in colorectal cancer: critical appraisal of pro-inflammatory bias and therapeutic implications

Abstract

We read with interest the article by Soundararajan et al , titled ‘Integration of lipidomics with targeted, single cell, and spatial transcriptomics defines an unresolved pro-inflammatory state in colon cancer’ published in Gut.1 The study presents a comprehensive analysis of lipid dysregulation in colorectal cancer (CRC), highlighting a pro-inflammatory lipidomic profile and defective lipid class switching. While the integration of multiomics data is commendable, we raise critical concerns about the study’s methodology, interpretation and translational relevance. 1. Prostaglandin (PGE2/PGD2) temporal roles neglected: The authors attributed defective resolution of inflammation in CRC to insufficient PGE2/PGD2 signalling and proposed therapeutic induction of lipid class switching. However, this hypothesis oversimplifies the role of prostaglandins. Studies by Serhan et al emphasised that lipid mediator dynamics were …