Study of 189 tumors finds a distinct cell mix in young-onset colorectal cancer

What happened

Scientists from Dana-Farber Cancer Institute, the Broad Institute and Mass General Brigham's Gene Lay Institute have identified biological features that may help explain why colorectal cancer can be more aggressive in younger adults, Dana-farber reported. The findings appeared in Nature Medicine, and the work was described as the largest study of its type.

The team examined 189 surgical tumor samples from patients aged 29 to over 90. Of these, 54 were diagnosed before age 50 and 135 at 50 or older. Applying single-nucleus RNA sequencing to frozen archived tissue, they profiled gene expression across over 850,000 cells. Instead of splitting patients into two age groups, they tracked traits that shifted gradually with age, controlling for sex, tumor stage and site, and earlier treatment.

In the most common subtype, tumors from younger patients contained notably more supporting and connective cells compared with cancer cells. The team checked this pattern against gene-activity data from 564 additional tumors and stained tissue images from 712 more. Tumors from younger patients also showed elevated activity of long non-coding RNAs and signs of stronger cell-to-cell signaling linked to invasion.

Context

According to the American Cancer Society, colorectal cancer diagnoses among people under 50 in the United States increased 2.9% annually from 2013 through 2022. The group's 2026 report names it the top cause of cancer death in that age bracket, and younger patients are more often diagnosed at later stages. Co-senior author Ramnik J. Xavier said the work lays groundwork for studying how chemicals from diet and gut microbes interact with these cell programs.