A novel study is shedding light on factors that may affect treatment response in patients with young-onset colorectal cancer. Researchers uncovered differences in transcriptional metabolic profiles and other drivers of disease, as well as immune profiles, between younger and older patients with colorectal cancer. These findings were presented by Vadehra et al at the 2023 ASCO Annual Meeting (Abstract 3509).
“This idea arose from my wanting to investigate the question of what factors at the metabolic level may be influencing the rise in young-onset colorectal cancer,” said Deepak Vadehra, DO, of the Gastrointestinal Center Roswell Park Comprehensive Cancer Center, as well as Co-Leader of the Adolescent/Young Adult Translational Research Group. “Our concept is a novel look at metabolic dysregulation. We used a unique bioinformatics-based approach that used the transcriptomic data to identify metabolic dysregulation. This identified affected pathways that may be clinically impactful and allow for targeting of those pathways and may give signals that could explain the reason for the poor outcomes in young-onset colorectal cancer.”
Study Details
Working with data from a total of 857 patients who had either colon adenocarcinoma or colorectal cancer, the investigators compared the transcriptional profiles of patients older than 50 against those of patients 50 or younger. Transcriptional profiling helps determine the degree to which genes influence the behavior of cells. The research team used this method to identify differences in metabolic flux and transcriptional dysregulation—processes that interfere with the normal functioning of various genes.
The team retrieved data from The Cancer Genome Atlas for 397 patients with colon adenocarcinoma and from the Oncology Research Information Exchange Network for 460 patients with colorectal cancer. Along with age, the groups were categorized by race, gender, tumor stage, and body mass index.
In younger patients, the data showed enriched NRAS and MYC oncogenes; mutations of both oncogenes are associated with the proliferation and metastasis of colorectal cancer. Younger patients also were found to have enriched metabolic pathways for amino acids and lipids—which can contribute to the development and progression of cancer—as well as enriched cellular processes.
The investigators found that older patients had upregulated pathways that increase both steroid hormone metabolism and kynurenine metabolism, which can contribute to the growth of cancer cells. But patients older than 50 years also had upregulated pathways associated with response to CTLA-4 and PD-L1 immune checkpoint inhibitors, which are commonly used for the treatment of metastatic colon cancer. This may indicate that older patients are more responsive to those therapies than younger patients.
The research team hopes the results of their study will help future studies zero in on new ways of treating colorectal cancer in younger patients.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
