Prognostic features and intratumor microbiome in surgically resected pancreatic head, body, and tail cancer patients.

Abstract

e16440 Background: This study aimed to investigate overall survival (OS) in patients with surgically resected pancreatic cancer and examined the distribution of intratumoral microbiomes across distinct sites within pancreatic tumors. Methods: Patients were selected from the Surveillance, Epidemiology, and End Results (SEER) registry (2000–2021 dataset). Kaplan-Meier survival analysis and multivariable Cox proportional hazards models were used to assess overall and site-specific survival outcomes. A retrospective analysis was initiated to verify prognostic factors related with survival in surgically resected pancreatic cancer patients. To compare differential profiles of intratumoral microbiota, 16S rRNA gene sequencing was conducted on tissue samples from 7 patients with pancreatic head cancer (PHC) and 7 with pancreatic body/tail cancer (PBTC). Correlations between microbiota and prognosis, as well as associated gene expression changes, were analyzed using data from The Cancer Genome Atlas (TCGA). The effect of microbiota on tumor metastasis was confirmed by a pulmonary metastasis model of mouse pancreatic cancer. Results: A total of 78,548 patients were identified. The OS of surgically resected patients with PBTC was significantly better than that of patients with PHC. Multivariate analysis showed that male, older age, pancreatic head location, M1 and stage IIB/III/IV were independent predictors of poorer survival. Retrospective analysis involved 162 patients of our center verified that OS of PBTC was significantly longer than PHC. Microbiota was detected in tumor tissue of pancreatic cancer patients. The microbial species diversity in PHC tissues was significantly higher than in PBTC tissues, with microbial compositions across six phylogenetic levels highlighting specific differences between PHC and PBTC patients. At the genus level, 17 bacterial genera were identified, among which Sphaerotilus and Dyella , significantly enriched in PBTC patients, were associated with improved survival, as indicated by TCGA survival data. Absence of these bacteria might contribute to immune deficiency, widespread activation of cancer-related pathways, and metabolic reprogramming. In vivo experiment proved that Sphaerotilus and Dyella could inhibit pulmonary metastasis of pancreatic cancer cells. Conclusions: Our study demonstrated that patients with pancreatic body/tail tumors had a notably longer median survival than those with tumors in the head region following surgical resection. Enrichment of Sphaerotilus and Dyella in PBTC was significantly associated with improved survival in pancreatic cancer patients. These findings suggest that intratumoral microbiota may play a role by modulating signaling-related genes and regulating immune status, highlighting its potential as a therapeutic target and prognostic marker of pancreatic cancer patients.