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Updated: Jul 31, 2025
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Published on: April 30, 2019
TPX2 expression as a negative predictor of gemcitabine efficacy in pancreatic cancer
Michael Guenther1,2, Sai Agash Surendran1, Michael Haas3
1Institute of Pathology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.
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.
Insights
High TPX2 expression in pancreatic cancer predicts poor outcomes with gemcitabine chemotherapy. This finding may guide treatment decisions for pancreatic ductal adenocarcinoma (PDAC) patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is overexpressed in human tumors, correlating with increased malignancy.
- The impact of TPX2 on gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC) remains uninvestigated.
Purpose of the Study:
- To investigate the prognostic significance of TPX2 expression in advanced and resected pancreatic ductal adenocarcinoma (PDAC).
- To determine if TPX2 expression predicts gemcitabine resistance in PDAC patients.
Main Methods:
- TPX2 expression was analyzed in tumor tissues from 139 advanced PDAC (aPDAC) and 400 resected PDAC (rPDAC) patients.
- Findings were validated using RNA sequencing data from 149 resected PDAC patients.
- Prognostic impact was assessed in relation to gemcitabine-based chemotherapy.
Main Results:
- High TPX2 expression was observed in 13.7% of aPDAC and 14.5% of rPDAC samples.
- High TPX2 expression correlated with significantly shorter progression-free survival (PFS) and overall survival (OS) in gemcitabine-treated aPDAC patients.
- High TPX2 expression was associated with shorter disease-free survival (DFS) and OS in patients receiving adjuvant gemcitabine for rPDAC.
- RNAseq validation confirmed these associations.
Conclusions:
- Elevated TPX2 expression is a potential negative predictor for gemcitabine-based chemotherapy in PDAC.
- TPX2 expression levels could inform clinical therapy decisions for PDAC patients undergoing palliative or adjuvant gemcitabine treatment.
