Serum Cytokine Profiling in Pancreatic Ductal Adenocarcinoma: A Pilot Study of Candidate Discriminators, Sex Differences and Altered Co-Regulation

Pancreatic ductal adenocarcinoma (PDAC) is rarely detected before the disease is advanced, and existing serum markers are insufficient for early detection. Its systemic immune alterations are incompletely characterized and rarely examined by sex. We measured 19 serum cytokines by bead-based multiplex assay in 22 patients with PDAC and 16 controls, comparing groups overall and separately in women and men, and examined co-regulation among them. In the full cohort, interleukin-7 (IL-7) was the only cytokine to discriminate patients from controls after correction for multiple testing. Adjustment for age strengthened this association, and IL-7 matched the discrimination of carbohydrate antigen 19-9 (CA19-9). After stratification by sex, IL-7 remained the only cytokine higher in women, though it did not survive correction within that subgroup, whereas in men, eight innate, T-helper 17 (Th17) and type I interferon cytokines (IL-1α, IL-1RA, IL-31, IFN-α, IL-17A, IL-17F, TNF-α, and TNF-β) separated patients from controls, although the male control group was small. The correlation network present in controls was largely absent in patients, which instead showed few associations centered on IL-2, IL-5 and IL-6. These findings identify IL-7 as a candidate discriminator of PDAC and show that the cytokines separating patients from controls differed by sex, warranting validation in a larger, sex-balanced cohort that also measures sex hormones.