Younger colorectal cancer patients have more stromal cells, study finds
Colorectal cancer in younger adults is increasingly characterized by a distinct tumor microenvironment that differs significantly from cases diagnosed in older populations, according to a study published October 29 in Nature Medicine. Researchers at Dana-Farber Cancer Institute and their partners found that colorectal tumors from younger patients contain a larger share of connective and supporting cells, known as stromal cells, than tumors from older patients.
The Cellular Differences in Younger Patients
The study offers a detailed look at how colorectal cancer in people under 50 may differ at the cellular level. Rather than simply splitting patients into “young” and “old” groups, researchers looked for features that changed gradually with age, adjusting for tumor location, stage, sex, and prior treatment. In tumors of the most common colorectal cancer subtype, younger patients had a significantly higher proportion of stromal cells relative to cancer cells.
Younger patients’ tumors also showed other distinct patterns of gene activity. Younger microsatellite stable (MSS) tumors exhibit an increased stromal-to-epithelial ratio, validated in 712 tumors. Increased inferred FN1, GDF, ACTIVIN and SPP1 interactions suggest enhanced tumor–stroma crosstalk, alongside increased lncRNA expression including poorly characterized transcripts. Genomic copy number alteration patterns were largely conserved across ages, with a trend toward greater intratumoral heterogeneity.
"I saw hope in that article." Patient Chris Causey and @KimmieNgMD, director of the @DFarberYoungCRC, speak with @NBC10Boston about a new study co-led by @DanaFarber showing important differences based on age in #ColorectalCancer tumors.https://t.co/ryEEa8Hgjs
Stromal Cells Shape Tumor Growth and Drug Resistance
Stromal cells form the structural neighborhood around a tumor, shaping how it grows, interacts with the immune system, and how well drugs reach the cancer. In other solid cancers, a high proportion of these cells has been linked to resistance to chemotherapy.
However, the study did not test whether these tumors resisted chemotherapy, and the link to resistance comes from research in other solid cancers. The findings are not a reason for patients to change their chemotherapy plans, but patients under 50 can ask their oncologist whether clinical trials for young-onset disease are available. The research shows that certain features are more common in younger patients’ tumors, but it does not prove that those features cause more aggressive disease. Future work will examine how these cellular changes affect cancer growth and spread, and how the cell programs interact with chemicals from the diet and with gut microbes.
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