Leukocyte telomere length and gut microbiome profiles in pancreatic ductal adenocarcinoma and at-risk conditions.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, highlighting the need for minimally invasive biomarkers capable of distinguishing it from related risk conditions. This study evaluated relative leukocyte telomere length (LTL) and gut microbiome profiles as potential biomarkers for PDAC. The study included 244 participants with PDAC (n = 37), chronic pancreatitis (CP; n = 56), type 2 diabetes mellitus (T2DM; n = 99), or no related risk conditions (controls; n = 52). LTL was measured by monochrome multiplex quantitative polymerase chain reaction (qPCR), while gut microbiome composition was assessed by 16S ribosomal RNA (rRNA) gene sequencing in a subset of participants with PDAC (n = 12), CP (n = 13), and controls (n = 7). LTL varied with age, sex, and smoking status. After adjustment for these factors, patients with PDAC had significantly longer LTL than controls (p = 0.029), whereas differences between PDAC and CP or T2DM were not significant. LTL showed limited ability to discriminate PDAC from controls (area under the receiver operating characteristic curve = 0.651) and was not associated with overall survival. Gut microbiome diversity and taxonomic composition did not differ significantly among the analyzed groups. These findings indicate that LTL has limited utility as a standalone diagnostic or prognostic biomarker for PDAC but may warrant further evaluation as a complementary marker in larger prospective studies. The exploratory microbiome findings also require validation in adequately powered cohorts.