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

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.

Experimental Verification on the Hypothesis about the Possibility of Molecular Diagnostics of Local Tumor Spread on the Lewis Lung Carcinoma Model

“…TUBB3 belongs to the family of tubulin proteins being part of microtubules and has been intensively studied as a possible predictor of the efficacy of antitumor agents from the taxane group [1][2][3][4][5]. The uniqueness of TUBB3 as a potential tumor-associated marker is that it is practically not detected in normal epithelial cells [6] and is expressed only at low intensity in endotheliocytes and macrophages [7].…”

Mass spectrometry-based proteomic analysis to characterize cisplatin induced early signaling events in head and neck squamous cell carcinoma

“… 29–32 Patients with high expression of TUBB3 exhibit poor survival rate and resistance to docetaxel, paclitaxel- and cisplatin-based chemotherapies. 24 , 33–37 Head and neck cancer patients positive for TUBB3 expression and undergoing induction chemotherapy with 5-Flurouracil (5-FU) and cisplatin and 5-FU, cisplatin and docetaxel exhibited lower response rate. In addition, they also showed a higher disease progression and reduction in overall survival rate compared to TUBB3-negative patients.…”

Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer

“…TUBB3 was also found both in GSE19860 and GSE3964. One research suggested that patients with high TUBB3 had a statistically significant poorer OS when undergoing docetaxelbased versus 5-FU/LV chemotherapeutic (21).…”