TPX2 expression as a negative predictor of gemcitabine efficacy in pancreatic cancer.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
05
01
2023
accepted:
21
04
2023
revised:
18
04
2023
medline:
30
6
2023
pubmed:
5
5
2023
entrez:
4
5
2023
Statut:
ppublish
Résumé
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. 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. 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. 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. The clinical trial registry identifier is NCT00440167.
Sections du résumé
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.
CLINICAL TRIAL REGISTRY
The clinical trial registry identifier is NCT00440167.
Identifiants
pubmed: 37142730
doi: 10.1038/s41416-023-02295-x
pii: 10.1038/s41416-023-02295-x
pmc: PMC10307892
doi:
Substances chimiques
Gemcitabine
0
TPX2 protein, human
0
Microtubule-Associated Proteins
0
Cell Cycle Proteins
0
Banques de données
ClinicalTrials.gov
['NCT00440167']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
175-182Informations de copyright
© 2023. The Author(s).
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