Association of high TUBB3 with resistance to adjuvant docetaxel-based chemotherapy in gastric cancer: translational study of ITACA-S

Maria Di Bartolomeo, Alessandra Raimondi, Fabiola Cecchi, Daniel V.T. Catenacci, Sarit Schwartz, Shankar Sellappan, Yuan Tian, Rosalba Miceli, Alessandro Pellegrinelli, Elisa Giommoni, Enrico Aitini, Francesca Spada, Gerardo Rosati, Alberto Marchet, Francesca Pucci, Alberto Zaniboni, Stefano Tamberi, Tiziana Pressiani, Gianni Sanna, Maurizio CantoreStefania Mosconi, Paola Bolzoni, Carmine Pinto, Lorenza Landi, Hector Josè Soto Parra, Luigi Cavanna, Salvatore Corallo, Antonia Martinetti, Todd A. Hembrough, Filippo Pietrantonio

Research output: Contribution to journalArticlepeer-review

Abstract

Background: No predictive markers for chemotherapy activity have been validated in gastric cancer (GC). The potential value of class III β-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.

Original languageEnglish
JournalTumori
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • adjuvant therapy
  • class III β-tubulin
  • Gastric cancer
  • taxane

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Association of high TUBB3 with resistance to adjuvant docetaxel-based chemotherapy in gastric cancer: translational study of ITACA-S'. Together they form a unique fingerprint.

Cite this