Distinct cellular and genetic differences in colorectal cancer in young patients

Researchers mapped age-related biological differences in colorectal tumors to investigate why the disease is increasingly affecting younger adults and can be more aggressive in them. The team analyzed 189 tumors from patients ages 29 to over 90, including 54 diagnosed before age 50, using single-nucleus RNA sequencing to measure gene activity in more than 850,000 tumor and other cells. Instead of simply comparing younger and older groups, they modeled changes across age while accounting for tumor location, stage, sex, and prior treatment, an approach intended to reveal gradual patterns that a simple age cutoff could miss.

In the most common colorectal cancer subtype, younger patients’ tumors contained a higher proportion of connective and supporting cells relative to cancer cells; this pattern was also found in independent tumor datasets and tissue images. Such cells have been associated with chemotherapy resistance in other solid cancers. The researchers also found greater activity of long non-coding RNAs, including poorly understood “dark” RNAs, and gene-activity patterns suggesting stronger signaling that may help cancer cells move and invade nearby tissue. The findings identify leads for studying early-onset disease, not proof that these features cause more aggressive cancer. The analysis captured relatively few immune cells, leaving age-related immune differences unresolved. Future work will test how the identified cell programs affect tumor growth and spread and whether they could guide prevention or treatment.