K-ras oncogene mutation as a prognostic marker in non-small cell lung cancer:: a combined analysis of 881 cases
K-ras oncogene mutation as a prognostic marker in non-small cell lung cancer:: a combined analysis of 881 cases
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DOI：
10.1093/carcin/20.8.1507
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发表时间：
1999-08-01
期刊：
影响因子：
4.7
通讯作者：
Geschwind, JF
中科院分区：
文献类型：
--
作者：
Huncharek, M;Muscat, J;Geschwind, JF
非小细胞肺癌（NSCLC）的治疗仍然不令人满意，大多数患者在诊断后5年内死于转移性疾病。对患者积极辅助治疗的改进选择可能有助于提高生存率。k-ras癌基因突变被认为是一种潜在的临床有用的预后生物标志物。本报告提出了一项荟萃分析的结果，以确定现有数据是否支持k-ras突变在NSCLC中的作用。8项已发表研究中881名非小细胞肺癌患者的2年生存数据采用基于方差的通用meta分析方法，采用置信区间进行分析。关注的结果是总结相对危险度（RI），反映k-ras突变阳性与k-ras突变阴性疾病相关的2年死亡风险。在计算RR之前，异质性分析显示Q = 15.52 （7 df, P = 0.03）。这表明在分析的研究中对效果的估计存在异质性。确定了可能的异质性来源，包括选择偏倚和各种其他非控制混杂来源。虽然当所有8项研究合并时，发现RR为2.35 (95% CI = 1.61-3.22)（支持k-ras突变的负面预后作用），但尚不清楚在调整其他已确定的预后指标（如分期）后，RR的大小是否会持续存在。现有的数据表明，k-ras突变可能与NSCLC的生存期缩短有关，尽管这一发现有待于精心设计的多变量分析来证实，该分析将调整已知预后指标的影响。
The treatment of non-small cell lung cancer (NSCLC) remains unsatisfactory, with most patients succumbing to metastatic disease within 5 years of diagnosis. Improved selection of patients for aggressive adjuvant therapy may contribute to improved survival. Mutation of the k-ras oncogene is considered a potentially clinically useful prognostic biomarker for this purpose. This report presents the results of a meta-analysis performed to determine whether the existing data support such a role for k-ras mutations in NSCLC. Two year survival data derived from 881 NSCLC patients in eight published studies were analyzed using a general variance-based meta-analytical method employing confidence intervals. The outcome of interest was a summary relative risk (RI,) reflecting the risk of death at 2 years associated with k-ras mutation-positive versus k-ras mutation-negative disease. Prior to calculation of RR,, analysis for heterogeneity showed Q to equal 15.52 (7 df, P = 0.03). This indicated heterogeneity across the analyzed studies in terms of their estimate of effect. Possible sources of heterogeneity were identified and included selection bias and various other sources of uncontrolled confounding. Although a RR, of 2.35 (95 % CI = 1.61-3.22) was found when all eight studies were combined (favoring a negative prognostic role for k-ras mutation), it is unclear whether the magnitude of the RR, would persist after adjusting for other well-established prognostic indicators (e.g. stage). The existing data suggest that k-ras mutation may be associated with shortened survival in NSCLC, although this finding awaits confirmation in well-designed multivariate analyses which adjust for the effect of known prognostic indicators.