Original Articles
Effects of TUBB3, TS and ERCC1 mRNA expressions on chemoresponse and clinical outcome of advanced gastric cancer by multiplex branched-DNA liquid chip technology
Abstract
Objective: To analyze the impacts of β-tubulin-III (TUBB3), thymidylate synthase (TS) and excision repair cross complementation group 1 (ERCC1) mRNA expressions on chemoresponse and clinical outcomes of patients with advanced gastric cancer (GC) treated with docetaxel (TXT)/cisplatin (CDDP)/fluorouracil (FU) (DCF) regimen chemotherapy.
Methods: The study population consisted of 48 patients with advanced GC. All patients were treated with DCF regimen palliative chemotherapy. The mRNA expressions of TUBB3, TS and ERCC1 of primary tumors were examined by multiplex branched-DNA liquid chip technology.
Results: The patients with low TUBB3 mRNA expression had significantly higher response rate to chemotherapy than patients with high TUBB3 expression (P=0.011). There were no significant differences between response rate and TS or ERCC1 expression pattern. Median overall survival (OS) and median time to progression (TTP) were significantly longer in patients with low TUBB3 mRNA expression (P=0.002, P<0.001). TS or ERCC1 expression was not correlated with TTP and OS. In the combined analysis including TUBB3, TS and ERCC1, the patients with 0 or 1 high expression gene had better response rate, TTP and OS than the remaining patients (all P<0.001). Multivariate analysis revealed that Eastern Cooperative Oncology Group (ECOG) ≥2 [hazard ratio (HR) =2.42, P=0.009] and TUBB3 (HR =2.34, P=0.036) mRNA expression significantly impacted on OS.
Conclusions: High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 may be a predictive and prognostic factor in patients with advanced GC treated with TXT-based chemotherapy. The combined evaluation of TUBB3, TS and ERCC1 expression can promote the individual treatment in advanced GC.
Methods: The study population consisted of 48 patients with advanced GC. All patients were treated with DCF regimen palliative chemotherapy. The mRNA expressions of TUBB3, TS and ERCC1 of primary tumors were examined by multiplex branched-DNA liquid chip technology.
Results: The patients with low TUBB3 mRNA expression had significantly higher response rate to chemotherapy than patients with high TUBB3 expression (P=0.011). There were no significant differences between response rate and TS or ERCC1 expression pattern. Median overall survival (OS) and median time to progression (TTP) were significantly longer in patients with low TUBB3 mRNA expression (P=0.002, P<0.001). TS or ERCC1 expression was not correlated with TTP and OS. In the combined analysis including TUBB3, TS and ERCC1, the patients with 0 or 1 high expression gene had better response rate, TTP and OS than the remaining patients (all P<0.001). Multivariate analysis revealed that Eastern Cooperative Oncology Group (ECOG) ≥2 [hazard ratio (HR) =2.42, P=0.009] and TUBB3 (HR =2.34, P=0.036) mRNA expression significantly impacted on OS.
Conclusions: High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 may be a predictive and prognostic factor in patients with advanced GC treated with TXT-based chemotherapy. The combined evaluation of TUBB3, TS and ERCC1 expression can promote the individual treatment in advanced GC.
