Huang Jin, Hu Huabin, Xie Yangchun, Tang Youhong, Liu Wei, Zhong Meizuo
Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2013 Jun;38(6):582-9. doi: 10.3969/j.issn.1672-7347.2013.06.006.
To analyze the impact of β-tubulin-III (TUBB3), thymidylate synthase (TS) and excision repair cross complementation group 1 (ERCC1) mRNA expression on chemoresponse and clinical outcome of patients with advanced gastric cancer treated with TXT/CDDP/FU (DCF) regimen chemotherapy.
The study population consisted of 48 patients with advanced gastric cancer. 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.
The patients with low TUBB3 mRNA expression had 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 ECOG (Eastern Cooperative Oncology Group)≥2 (HR=2.42, P=0.009) and TUBB3 (HR=2.34, P=0.036) mRNA expression significantly impacted on OS.
High TUBB3 mRNA expression is correlated with resistance to DCF regimen chemotherapy. TUBB3 might be a predictive and prognostic factor in patients with advanced gastric cancer treated with TXT-based chemotherapy. The combined evaluation of TUBB3, TS and ERCC1 expression can promote the individual treatment in advanced gastric cancer.
分析β-微管蛋白III(TUBB3)、胸苷酸合成酶(TS)和切除修复交叉互补基因1(ERCC1)mRNA表达对采用多西他赛/顺铂/氟尿嘧啶(DCF)方案化疗的晚期胃癌患者化疗反应及临床结局的影响。
研究对象为48例晚期胃癌患者。所有患者均接受DCF方案姑息化疗。采用多重分支DNA液相芯片技术检测原发肿瘤中TUBB3、TS和ERCC1的mRNA表达。
TUBB3 mRNA低表达患者的化疗反应率高于TUBB3高表达患者(P = 0.011)。反应率与TS或ERCC1表达模式之间无显著差异。TUBB3 mRNA低表达患者的中位总生存期(OS)和中位疾病进展时间(TTP)显著更长(P = 0.002,P < 0.001)。TS或ERCC1表达与TTP和OS无关。在包括TUBB3、TS和ERCC1的联合分析中,0或1个高表达基因的患者比其余患者具有更好的反应率、TTP和OS(所有P < 0.001)。多因素分析显示,东部肿瘤协作组(ECOG)≥2(HR = 2.42,P = 0.009)和TUBB3(HR = 2.34,P = 0.036)mRNA表达对OS有显著影响。
TUBB3 mRNA高表达与DCF方案化疗耐药相关。TUBB3可能是接受基于多西他赛化疗的晚期胃癌患者的预测和预后因素。联合评估TUBB3、TS和ERCC1表达可促进晚期胃癌的个体化治疗。