Class III β-tubulin is a predictive marker for taxane-based chemotherapy in recurrent and metastatic gastric cancer

Abstract

BackgroundClass III β-tubulin (TUBB3) is a prognostic marker in various tumors, but the role of TUBB3 in advanced gastric cancer is not clearly defined. We analyzed the significance of TUBB3 expression, along with that of excision repair cross-complementation group 1 (ERCC1) in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy.MethodsWe reviewed the cases of 146 patients with advanced gastric adenocarcinoma who received taxane-based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun Hospital (Gwangju, Korea). Immunohistochemical staining for TUBB3 and ERCC1 was performed using paraffin wax-embedded tumor tissues. We evaluated the patients’ response to chemotherapy, progression-free survival (PFS), and overall survival (OS).ResultsIn total, 146 patients with advanced gastric cancer received docetaxel and cisplatin (n = 15) or paclitaxel and cisplatin (n = 131). The median PFS was significantly shorter for patients with high-level TUBB3 expression than for patients with low-level TUBB3 expression (3.63 vs. 6.67 months, P = 0.001). OS was not associated with TUBB3 expression (13.1 vs. 13.1 months, P = 0.769). By multivariate analysis, only TUBB3 was related to a shorter PFS (HR 2.74, 95% CI 1.91-3.91, P = 0.001). Patients with high-level ERCC1 expression showed a lower response rate than patients with low-level ERCC1 expression (24 vs. 63.2%, P = 0.001); however, ERCC1 had no clinical effect on PFS or OS.ConclusionsTUBB3 was a strong predictive marker in recurrent and metastatic gastric cancer patients receiving taxane-based first-line palliative chemotherapy. No clinical impact of ERCC1 was evident in this setting.

Molecular mechanisms of synergistic action of Ramucirumab and Paclitaxel in Gastric Cancers cell lines

“…www.nature.com/scientificreports www.nature.com/scientificreports/ The combined regimen represents a promising option to increase the efficacy of PTX and to prevent its resistance also in patients receiving taxane-based first-line palliative chemotherapy 14 . Although PTX is widely used as a first-line agent in chemotherapies, several studies indicate factors such as microtubule organization, EMT phenotype and apoptotic resistance as the main causes of resistance to treatment with this drug [15][16][17][18][26][27][28][29][30] . In epithelial tumor cells, the binding of VEGFA to VEGFR2 sustains autocrine loop affecting cell growth and migration.…”

“…PTX exerts its action also by promoting tubulin polymerization and inhibiting tubulin depolymerization. Microtubule disorganization, decreased responses to antimitotic treatments, and apoptotic process failure can induce acquired resistance to PTX in advanced gastric cancer [15][16][17][18][19] .…”

Molecular profiling in gastric cancer: Examining potential targets for chemotherapy

“…As more biomarkers are identified, it is possible that multiple molecular targets will be used to evaluate the potential efficacy of a single chemotherapeutic agent. For example, a recent study by Hwang et al shows that class III β‐tubulin is also a predictor for taxane‐based therapy in gastric cancer. Therefore it would be logical to consider both the taxane target β‐tubulin together with the drug efflux pump PGP levels when determining taxane responses.…”

Expression of Class III Beta-tubulin Predicts Prognosis in Patients with Cisplatin-resistant Bladder Cancer Receiving Paclitaxel-based Second-line Chemotherapy

“…We cannot explain the reason for the discrepancy between UC and other malignancies regarding the pathological significance of TUBB3. However, several other studies on a variety of malignancies have also repeated that TUBB3 expression is not associated with stage or metastatic status (7,(26)(27)(28). Finally, we speculate that methodological differences, such as antibodies used, method of evaluation, and background of patients, may contribute to this discrepancy, and that the pathological roles of TUBB3 in invasion and metastasis are minimal in UC.…”