BackgroundTargeting protein for Xenopus kinesin-like protein 2 (TPX2) overexpression in human tumours is associated with increased malignancy. Its effect on gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC) has not been studied yet.MethodsThe prognostic impact of TPX2 expression was examined in the tumour tissue of 139 patients with advanced PDAC (aPDAC) treated within the AIO-PK0104 trial or translational trials and of 400 resected PDAC (rPDAC) patients. The findings were validated using RNAseq data of 149 resected PDAC patients.ResultsIn the aPDAC cohorts, 13.7% of all samples showed high TPX2 expression, conferring significantly shorter progression-free survival (PFS, HR 5.25,P< 0.001) and overall survival times (OS, HR 4.36,P< 0.001) restricted to gemcitabine-based treated patients (n= 99). In the rPDAC cohort, 14.5% of all samples showed high TPX2 expression, conferring significantly shorter disease-free survival times (DFS, HR 2.56,P< 0.001) and OS times (HR 1.56,P= 0.04) restricted to patients treated with adjuvant gemcitabine. RNAseq data from the validation cohort confirmed the findings.ConclusionsHigh TPX2 expression may serve as a negative predictor of gemcitabine-based palliative and adjuvant chemotherapy in PDAC and could be used to inform clinical therapy decisions.Clinical trial registryThe clinical trial registry identifier is NCT00440167.