Expression of choline kinase alpha to predict outcome in patients with early-stage non-small-cell lung cancer:: a retrospective study
Expression of choline kinase alpha to predict outcome in patients with early-stage non-small-cell lung cancer:: a retrospective study
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DOI：
10.1016/s1470-2045(07)70279-6
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发表时间：
2007-10-01
期刊：
影响因子：
51.1
通讯作者：
Lacal, Juan Carlos
中科院分区：
文献类型：
--
作者：
Ramirez de Molina, Ana;Sormentero-Estrada, Jacinto;Lacal, Juan Carlos
背景：仍然需要足够的预后标志物来预测肺癌患者的预后。本研究的目的是评估胆碱激酶α(ChOKα)基因的表达是否可以识别具有不同预后的患者。Choka是一种参与细胞代谢和增殖的酶，在包括肺癌在内的多种人类肿瘤的癌基因介导的转化中发挥作用。方法将60例在同一中心接受手术切除的非小细胞肺癌患者作为训练组。我们使用实时逆转录聚合酶链式反应(RT-PCR)来检测CHOKα基因的表达，并分析CHOKα基因的表达与可评估患者的生存之间的关系。此外，第二组来自不同医院的120名非小细胞肺癌患者作为验证组被纳入研究。我们对所有167名拥有可用组织的患者进行了全面的分析，以确定未来研究的截断点。主要终点是肿瘤特异性存活率和无复发存活率。结果训练组60名患者中有7名因组织不足而无法评估。在53例可评估的患者中，ChokA过度表达的界值由受试者根据曲线(ROC)方法确定。Chokα表达高于ROC定义的临界值的25例患者的4年肺癌特异性生存率为54-43%(95%CI 28.24-80.61)，低于该临界值的28例患者的4年肺癌特异性生存率为88.27%(75.79-100)(危险比[HR]3.14[0.83-11.88]，p=0.07)。在验证组中，120名入选患者中有6名因组织不足而无法评估。在其他114名患者中，Choka表达高于ROC定义的临界值的患者的4年肺癌特定生存率为46-66%(32.67-59.65)，而Choka浓度低于临界值的患者(HR为1.87[1-01-3.46]，p=0.04)的4年肺癌特异性生存率为67.01%(50.92-81.11)。一项对所有167名患者的全球分析进一步证实了CHOKα过度表达之间的联系。NSCLC患者的临床预后较差：Chokα表达高于ROC定义的临界值的4年肺癌特异性生存率为49.00%(36.61-60.38)，而Choka浓度低于临界值的患者为70.52%(59.80-76.75)(HR 1.98[1.14-3.45]，p=0.01)。总体分析证实，当Chokα被用作早期NSCLC患者无复发和高癌特异性生存的独立预测因素时，Chokα表达的截止点应该是健康组织中浓度的1.91倍。解释Chokα表达是一个新的预后因素，可以用来帮助识别早期NSCLC患者可能有高复发风险，并识别预后良好的患者，他们可以接受不那么激进的治疗选择或避免辅助系统治疗。抑制肺癌患者Chokα表达或活性的新疗法应进一步研究。
Background Adequate prognostic markers to predict outcome of patients with lung cancer are still needed. The aim of this study was to assess whether choline kinase alpha (ChoK alpha) gene expression could identify patients with different prognoses. ChoKa is an enzyme involved in cell metabolism and proliferation and has a role in oncogene-mediated transformation in several human tumours, including lung cancer.Methods 60 patients with non-small-cell lung cancer (NSCLC) who had undergone surgical resection in a single Centre were enrolled into the study as the training group. We used real-time reverse-transcriptase PCR (RT-PCR) to measure ChoK alpha gene expression and analyse the association between ChoK alpha expression and survival in evaluable patients. Additionally, a second group of 120 patients with NSCLC from a different hospital were enrolled into the study as the validation group. We did an overall analysis of all 167 patients who had available tissue to confirm the cut-off point for future studies. The primary endpoints were hing-cancer-specific survival and relapse-free survival.Findings Seven of the 60 patients in the training group were not evaluable due to insufficient tissue. In the 53 evaluable patients, the cut-off for those with ChoKa overexpression was defined by receiver operator under the curve (ROC) methodology. 4-year lung-cancer-specific survival was 54-43% (95% CI 28.24-80.61) for 25 patients with ChoK alpha expression above the ROC-defined cut-off compared with 88.27% (75.79-100) for 28 patients with concentrations of the enzyme below this cut-off (hazard ratio [HR] 3.14 [0.83-11.88], p=0.07). In the validation group, six of the 120 enrolled patients were not evaluable due to insufficient tissue. For the other 114 patients, 4-year lung-cancer-specific survival was 46-66% (32.67-59.65) for those with ChoKa expression above the ROC-defined cut-off compared with 67.01% (50.92-81.11) for patients with concentrations of ChoKa below the cut-off (HR 1.87 [1-01-3.46], p=0.04). A global analysis of all 167 patients further confirmed the association between ChoK alpha overexpression. and worse clinical outcome of patients with NSCLC: 4-year lung-cancer-specific survival for ChoK alpha expression above the ROC-defined cut-off was 49.00% (36.61-60.38) compared with 70.52% (59.80-76.75) for those with concentrations of ChoKa below the cut-off (HR 1.98 [1.14-3.45], p=0.01). The overall analysis confirmed the cut-off for ChoK alpha expression should be 1.91-times higher than concentrations noted in healthy tissues when ChoK alpha is used as an independent predictive factor of relapse-free and hing-cancer-specific survival in patients with early-stage NSCLC.Interpretation ChoK alpha expression is a new prognostic factor that could be used to help identify patients with early-stage NSCLC who might be at high risk of recurrence, and to identify patients with favourable prognosis who could receive less aggressive treatment options or avoid adjuvant systemic treatment. New treatments that inhibit ChoK alpha expression or activity in patients with lung cancer should be studied further.