Department of Thoracic Surgery, Jiangsu Cancer Hospital, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
PLoS One. 2013;8(1):e54970. doi: 10.1371/journal.pone.0054970. Epub 2013 Jan 25.
The prognostic significance of p16 promoter hypermethylation in patients with non-small cell lung cancer (NSCLC) is still controversial. This analysis presents pooled estimates of the association to better elucidate whether p16 methylation has a prognostic role in NSCLC.
Relevant studies were identified by searching PubMed, Embase and Web of Science databases until June 2012. The association of p16 methylation with both overall survival (OS) and disease-free survival (DFS) was preformed. Studies were pooled and summary hazard ratios (HR) were calculated. Subgroup analyses, sensitivity analysis and publication bias were also conducted.
A total of 18 studies containing 2432 patients met the inclusion criteria and had sufficient survival data for quantitative aggregation. The results showed that p16 methylation was an indicator of poor prognosis in NSCLC. The HR was 1.36 (95% CI: 1.08-1.73, I(2) = 56.7%) and 1.68 (95% CI: 1.12-2.52, I(2) = 38.7%) for OS and DFS, respectively. Subgroup analyses were carried out. The HRs of fresh and paraffin tissue were 1.50 (95% CI: 1.11-2.01) and 1.10 (95% CI: 0.77-1.57). The pooled HR was 1.40 (95% CI: 1.02-1.92) for methylation-specific PCR (MSP) and 1.26 (95% CI: 0.87-1.82) for quantitative MSP (Q-MSP). The combined HR of the 16 studies reporting NSCLC as a whole indicated that patients with p16 hypermethylation had poor prognosis. No significant association was found when adenocarcinoma subtype pooled. When seven studies on DFS were aggregated, the HR was 1.68 (95% CI: 1.12-2.52) without significant heterogeneity. Moreover, no obvious publication bias was detected on both OS and DFS.
The meta-analysis findings support the hypothesis that p16 methylation is associated with OS and DFS in NSCLC patients. Large well-designed prospective studies are now needed to confirm the clinical utility of p16 methylation as an independent prognostic marker.
p16 启动子甲基化在非小细胞肺癌（NSCLC）患者中的预后意义仍存在争议。本分析对相关研究进行了汇总分析，以更好地阐明 p16 甲基化在 NSCLC 中是否具有预后作用。
通过检索 PubMed、Embase 和 Web of Science 数据库，截至 2012 年 6 月，确定了相关研究。对 p16 甲基化与总生存（OS）和无病生存（DFS）的相关性进行了分析。对研究进行了汇总，并计算了汇总风险比（HR）。还进行了亚组分析、敏感性分析和发表偏倚分析。
共有 18 项研究包含 2432 例患者符合纳入标准，并具有足够的生存数据进行定量汇总。结果表明，p16 甲基化是 NSCLC 预后不良的指标。OS 和 DFS 的 HR 分别为 1.36（95%CI：1.08-1.73，I²=56.7%）和 1.68（95%CI：1.12-2.52，I²=38.7%）。进行了亚组分析。新鲜组织和石蜡组织的 HR 分别为 1.50（95%CI：1.11-2.01）和 1.10（95%CI：0.77-1.57）。MSP 检测的汇总 HR 为 1.40（95%CI：1.02-1.92），Q-MSP 检测的汇总 HR 为 1.26（95%CI：0.87-1.82）。16 项报告 NSCLC 整体情况的研究的合并 HR 表明，p16 过度甲基化的患者预后不良。在合并腺癌亚组时，未发现显著相关性。当汇总 7 项关于 DFS 的研究时，HR 为 1.68（95%CI：1.12-2.52），无明显异质性。此外，OS 和 DFS 均未发现明显的发表偏倚。
荟萃分析结果支持 p16 甲基化与 NSCLC 患者 OS 和 DFS 相关的假设。目前需要进行大型、精心设计的前瞻性研究，以确认 p16 甲基化作为独立预后标志物的临床实用性。
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