TPX2 expression as a negative predictor of gemcitabine efficacy in pancreatic cancer
Menée à partir d'échantillons tumoraux prélevés sur 539 patients atteints d'un adénocarcinome canalaire du pancréas puis validée à partir de données de séquençage de l'ARN d'échantillons tumoraux issus de patients traités par chirurgie, cette étude met en évidence une association entre un niveau d'expression élevé de la protéine TPX2 et une faible efficacité de la gemcitabine en traitement adjuvant ou palliatif
Background : Targeting 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.
Methods : The 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.
Results : In 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.
Conclusions : High 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.
British Journal of Cancer , article en libre accès, 2023