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

Autor: Di Bartolomeo M; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Raimondi A; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Cecchi F; NantOmics, Rockville, MD., Catenacci DVT; Department of Medicine, University of Chicago, Chicago, IL., Schwartz S; NantOmics, Rockville, MD., Sellappan S; NantOmics, Rockville, MD., Tian Y; NantOmics, Rockville, MD., Miceli R; Department of Medical Statistics, Biometry, and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Pellegrinelli A; Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Giommoni E; Medical Oncology, Azienda Ospedaliera-Università Careggi, Firenze, Italy., Aitini E; Medical Oncology, Ospedale di Suzzara, Mantova, Italy., Spada F; Gastrointestinal Oncology and Neuroendocrine Tumors, Istituto Oncologico Europeo, Milan, Italy., Rosati G; Medical Oncology, Azienda Ospedaliera 'San Carlo,' Potenza, Italy., Marchet A; Surgery, Oncology and Gastroenterology Department, Azienda Ospedaliera di Padova, Padova, Italy., Pucci F; Medical Oncology, Azienda Ospedaliera di Parma, Parma, Italy., Zaniboni A; Oncology Department, Istituto Ospedaliero Fondazione Poliambulanza, Brescia, Italy., Tamberi S; Oncology Department, AUSL Romagna, Ravenna, Italy., Pressiani T; Medical Oncology and Hematology, Istituto Clinico Humanitas, Rozzano, Milan, Italy., Sanna G; Medical Oncology, Istituto Ospedaliero dell'Università di Sassari, Sassari, Italy., Cantore M; Medical Oncology, Azienda Ospedaliera 'Carlo Poma,' Mantova, Italy., Mosconi S; Medical Oncology, ASST Papa Giovanni XXIII, Bergamo, Italy., Bolzoni P; Medical Oncology, Presidio Ospedaliero 'Serbelloni' di Gorgonzola, Melegnano, Italy., Pinto C; Medical Oncology, Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia, Reggio Emilia, Italy., Landi L; Medical Oncology, Presidio Ospedaliero di Livorno, Livorno, Italy., Soto Parra HJ; Medical Oncology, Policlinico Vittorio Emanuele, Presidio Gaspare Rodolico, Catania, Italy., Cavanna L; Oncology-Hematology Department, Ospedale Civile 'Guglielmo da Saliceto,' Piacenza, Italy., Corallo S; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Martinetti A; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Hembrough TA; NantOmics, Rockville, MD., Pietrantonio F; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy.
Jazyk: angličtina
Zdroj: Tumori [Tumori] 2021 Apr; Vol. 107 (2), pp. 150-159. Date of Electronic Publication: 2020 Jun 11.
DOI: 10.1177/0300891620930803
Abstrakt: 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.
Databáze: MEDLINE