Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer

The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) belongs to the tumor necrosis factor ligand superfamily, which was shown to play an important role in inflammatory and malignant gastrointestinal diseases, including colitis or colorectal cancer. However, in contrast to other members of the TNF ligand superfamily, its role as a biomarker in pancreatic cancer is currently unknown. We analyzed serum levels of A proliferation-inducing ligand (APRIL) and TWEAK in 134 patients with pancreatic cancer. Results were compared with 50 healthy controls and correlated with clinical data. Intratumoral expression of APRIL and TWEAK in pancreatic cancer was analysed using the datasets made available by the TCGA-LIHC project. APRIL serum levels were significantly elevated in patients with pancreatic cancer compared to healthy controls, which is in line with previous findings. Notably, the diagnostic accuracy of circulating APRIL levels was similar to CA19-9, an established tumor marker for pancreatic cancer. In contrast, serum concentrations of TWEAK were decreased in pancreatic cancer patients. Interestingly, no differences in TWEAK concentrations became apparent between different clinical subgroups of pancreatic cancer. Moreover, within our cohort of patients, TWEAK levels did not correlate with the patients' prognosis and the diagnostic as well as prognostic potential of TWEAK was lower than CA 19-9, when analyzed in this setting. Finally, using data from the TCGA-LIHC project, we demonstrate that expression levels of TWEAK and APRIL represent prognostic markers for patients' survival according to Kaplan-Meier curve analyses. TWEAK and APRIL serum concentrations are regulated differently in patients with pancreatic cancer, highlighting diverse roles of variant TNF ligands in this type of cancer.