Colorectal cancer is the second leading cause of death in the United States and, the third most common cancer in the world, causing a massive number of deaths every year globally. Research at the University of South Florida (USF) and Tampa General Hospital (TGH) Cancer Institute has revealed a potential association between a Western diet, one dependent on ultra-processed foods like ‘bad’ oils leads to chronic inflammation that fuels tumors.
Now the researchers have already made considerable advances in colorectal cancer. Yeatman pointed out the findings and highlighted the urgency to rethink the constituents of the typical Western diet consisting of too many added sugars, saturated fats, highly processed foods, man-made chemicals, and inflammatory seed oils.
It is well-known that patients with bad diets have elevated levels of inflammation in their bodies, said Dr. Timothy Yeatman. He is a renowned physician-scientist and professor of surgery at the USF Health Morsani College of Medicine and associate center director for Translational Research and Innovation at the TGH Cancer Institute. He also mentioned that as we are witnessing the tumor, cancer is like a persistent wound that is not healing, and our body is not able to manage the wound due to the presence of chronic inflammation which acts as a huddle for immune response. As a result, it suppresses our immune system and ultimately promotes cancer growth.
“It is excellent if one can use the power of a human immune system to drastically change the tumor microenvironment and return one to health and wellness,” said Yeatman. But not if the inflammation itself is covered up by inflammatory lipids from processed foods that we consume.
The molecules are hard to see, but Halade used one of the most sensitive analytical techniques to find hidden lipids in 162 tumor samples from patients at Tampa General Hospital. After removing the tumors, these molecules were frozen in his laboratory within 30 minutes and they were handed over to his laboratory by USF and TGH Cancer Institute’s Biobank, working in conjunction with USF Health Colorectal Surgery and the Gastrointestinal Oncology Program at TGH Cancer Institute.
Dr. Timothy Yeatman and team supervised untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis on 40 paired human colorectal cancer (CRC) and normal samples along with targeted and quantitative LC-MS/MS analysis on 81 paired samples. By integrating lipidomics the quantitative reverse transcription-PCR, large-scale gene expression, and spatial transcriptomics with public scRNA-seq data considered the patterns, expression, and cellular localization of genes to elaborate in lipid mediator production and modification.
Targeted analysis revealed a significant imbalance of pro-inflammatory mediators in CRC, with a striking deficiency in resolving lipid mediators. Tumors showed higher levels of arachidonic acid derivatives along with overexpression of genes encoding their synthetic enzymes and receptors but displayed poor expression of genes involved in pro-resolving mediators like lipoxins (LXA4, LXB4) and their associated receptors. These results indicate that defective lipid class switching is potentially linked to inadequate PGE2/PGD2 levels that contribute to CRC pathology.
In conclusion, the lipidomic profile of CRC tumors is marked by a distinct pro-inflammatory bias and a deficiency in endogenous resolving mediators due to impaired lipid class switching. These insights open avenues for “resolution medicine” a novel therapeutic strategy aimed at inducing or supplementing resolution pathways to combat CRC.
Reference: Soundararajan R, Maurin MM, Rodriguez-Silva J, et al. Integration of lipidomics with targeted, single-cell, and spatial transcriptomics defines an unresolved pro-inflammatory state in colon cancer. Gut. 2024;0:1–18. doi:10.1136/gutjnl-2024-332535
