Tumor microbiome profiles in pancreatic cancer differ by age of onset
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CHICAGO — The microbiome profile of early-onset pancreatic adenocarcinoma is distinct from that of average-onset disease, according to findings presented at ASCO Annual Meeting.
Early-onset tumors appeared enriched for several microbial genera associated with pancreatic diseases, a finding researchers called “significant” and worthy of additional study.
“The alpha diversity — essentially the breadth, or richness of the microbiome spectrum — was more diverse in early-onset pancreatic cancer,” Suneel Kamath, MD, gastrointestinal oncologist at Cleveland Clinic, told Healio. “This makes sense because, when we’re young, our immune systems likely start out very broad to try to protect us. As we get older, our immune systems are more experienced and become more targeted.”
Incidence of early-onset gastrointestinal cancers — including pancreatic cancers — has increased steadily over the last few decades.
The underlying pathogenesis is poorly understood; however, research increasingly has focused on the tumor microbiome because of its effects on tumor development and outcomes, according to study background.
“We always try to use our clinical experience to inform what we should be investigating in the lab,” Kamath said. “We really want to understand if there is a unique signature for young-onset GI cancers — and, in this case, pancreatic cancer — that we can use to identify more effective treatments or better screening strategies that may detect these cancers earlier.”
Kamath and colleagues examined microbiome profiles of resected pancreatic adenocarcinoma specimens from Cleveland Clinic and Roswell Park Comprehensive Cancer Center repositories.
Samples had been resected from individuals with early-onset disease (younger than 50 years; n = 24) or average-onset disease (older than 50 years; n = 20).
Researchers used shotgun metagenomic sequencing to characterize the tissue microbiome of each sample.
The analysis included 63 tissue specimens — 13 tumor specimens and 10 adjacent normal specimens from individuals with early-onset disease, and 20 tumor specimens and 20 adjacent normal specimens from individuals with average-onset disease.
Investigators observed significantly higher alpha diversity in early-onset tumor specimens compared with adjacent normal tissue (P = .02) and average-onset specimens (P = .0062).
Analysis showed no significant difference in alpha diversity between average-onset tumor samples vs. adjacent normal tissue.
Researchers observed significantly different diversity of genera between all groups (P < .05).
The majority of species did not overlap between early-onset and average-onset tumor specimens (85.8%), or between early-onset tumor specimens and normal tissue (71.6%).
Results showed significant variation of tumor microbiome between early-onset and average-onset tumor samples.
Early-onset tumor tissue appeared more enriched for Enterobacter (10.8% vs. 7.19%), Neisseria (2% vs. 1.44%) and Escherichia (0.04% vs. 0.01%) genera, whereas average-onset tumor tissue appeared enriched in Klebsiella (51.42% vs. 50.17%) and Bacillus (4.5% vs. 3.59%) genera (P < .05 for all).
“These variations are very important to identify, and they are a great starting point,” Kamath said. “However, we’re definitely looking to continue this research in larger cohorts, in collaboration with other centers, to further validate these findings.”
The findings contribute to “an evolving story” of the immune signature for early-onset cancer, Kamath added.
“Ultimately, we want to know if we can identify differences between young individuals who don’t have pancreatic cancer vs. those who do,” Kamath said. “That is the most important question, and that may help us identify biomarkers that we could use as a screening tool in that population.”
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Jayakrishnan T, et al. Abstract 4016. Presented at: ASCO Annual Meeting; May 31-June 4, 2024.
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