Association of high TUBB3 with resistance to adjuvant docetaxel-based chemotherapy in gastric cancer: translational study of ITACA-S.
Tumori
; 107(2): 150-159, 2021 Apr.
Article
en En
| MEDLINE
| ID: mdl-32522106
ABSTRACT
BACKGROUND:
No predictive markers for chemotherapy activity have been validated in gastric cancer (GC). The potential value of class III ß-tubulin (TUBB3) as biomarker for prognosis and resistance to taxane-based therapy was reported.METHODS:
We analyzed GC samples of patients enrolled in the Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S), a randomized adjuvant study comparing 5-fluorouracil/leucovorin (5-FU/LV) and docetaxel-based sequential chemotherapy. TUBB3 was quantitated by selected reaction monitoring mass spectrometry and patients were stratified using a threshold of 750 attomoles per microgram (amol/µg). Cox proportional modeling and Kaplan-Meier survival analysis were used to assess the impact of TUBB3 expression on overall survival (OS) and disease-free survival.RESULTS:
Patients with TUBB3 protein levels >750 and <750 amol/µg were 21.9% and 78.1%, respectively, and were well-balanced between treatment arms. TUBB3 protein levels were not prognostic. Whereas no survival differences according to the 2 arms were observed in the subgroup with low TUBB3 expression (5-year OS 47% vs 40%; p = 0.44), patients with high TUBB3 had a clinically meaningful poorer OS when receiving docetaxel-based versus 5-FU/LV chemotherapy (5-year OS 31% vs 54%; p = 0.09), with a statistically significant interaction between TUBB3 and treatment (p = 0.049).CONCLUSIONS:
The quantification of TUBB3 might be considered as a negative predictive biomarker of benefit from taxane-based therapy in GC. Studies are needed to evaluate its role in the neoadjuvant setting.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Tubulina (Proteína)
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Adenocarcinoma
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Protocolos de Quimioterapia Combinada Antineoplásica
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Resistencia a Antineoplásicos
Tipo de estudio:
Clinical_trials
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Tumori
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia