Dr Kamath on the Tumor Microbiome of Early- and Average-Onset PDAC

Suneel Kamath, MD, assistant professor, medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, discusses tumor microbiome differences in early-onset vs average-onset pancreatic ductal adenocarcinoma (PDAC).

Notably, at the 2024 ASCO Annual Meeting, investigators presented data from an investigation on the tumor microbiome differences between early-onset and average-onset disease. The study used resected pancreatic cancer specimens categorized by the age of diagnosis and performed shotgun metagenomic sequencing to identify bacterial and fungal microbiomes. The key findings revealed that early-onset PDAC exhibited higher bacterial alpha diversity, and average-onset PDAC showed higher fungal alpha diversity. Additionally, significant differences in beta diversity and the relative abundance of top genera were observed between early- and average-onset disease, indicating distinct microbiome signatures.

The findings indicated that higher bacterial diversity in early-onset PDAC correlated with better survival, highlighting the microbiome’s potential as a prognostic biomarker. However, the study faced limitations, including selection bias due to the need for surgically resected specimens and inherent challenges with shotgun sequencing. Despite these limitations, the study provides evidence supporting the role of the microbiome in PDAC, with potential implications for screening, predicting therapy responses, and prognostication.

Kamath says that investigators examined specimens from 44 patients, including 24 with early-onset PDAC and 20 with average-onset disease. Investigators compared specimens from the tumors with those from the adjacent normal tissues, Kamath reports, sharing that findings revealed that the early-onset group exhibited a higher degree of alpha diversity in their pancreatic cancer microbiomes compared with the microbiomes of both adjacent normal tissue and the average-onset group. This indicates that a higher degree of alpha diversity might reflect a more robust and varied microbiome, potentially indicating a broader and richer immune system profile typical of younger individuals, according to Kamath.

Additionally, researchers identified that certain bacterial species were more prevalent in early-onset pancreatic cancer, specifically enterobacter, neisseria, and escherichia genera, he explains. In contrast, Klebsiella and Bacillus genera were more commonly found in average-onset pancreatic cancer, Kamath concludes.