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The Prognostic Value of Epigenetic Silencing of p16 Gene in NSCLC Patients: A Systematic Review and Meta-Analysis

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  • Zhang Lou-Qian
  • Yin Rong
  • Li Ming
  • Yang Xin
  • Jiang Feng
  • Xu Lin

Abstract

Background: 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. Methods: 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. Results: 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, I2 = 56.7%) and 1.68 (95% CI: 1.12–2.52, I2 = 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. Conclusion: 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.

Suggested Citation

  • Zhang Lou-Qian & Yin Rong & Li Ming & Yang Xin & Jiang Feng & Xu Lin, 2013. "The Prognostic Value of Epigenetic Silencing of p16 Gene in NSCLC Patients: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-7, January.
    • Handle: RePEc:plo:pone00:0054970
    DOI: 10.1371/journal.pone.0054970
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    References listed on IDEAS

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    1. Bo Zhang & Wei Zhu & Ping Yang & Tao Liu & Mei Jiang & Zhi-Ni He & Shi-Xin Zhang & Wei-Qing Chen & Wen Chen, 2011. "Cigarette Smoking and p16INK4α Gene Promoter Hypermethylation in Non-Small Cell Lung Carcinoma Patients: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 6(12), pages 1-9, December.
    2. Nur Sabrina Sapari & Marie Loh & Aparna Vaithilingam & Richie Soong, 2012. "Clinical Potential of DNA Methylation in Gastric Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 7(4), pages 1-8, April.
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    1. Hanyu Cao & Si Wang & Zhenyu Zhang & Jiangyan Lou, 2016. "Prognostic Value of Overexpressed p16INK4a in Vulvar Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-11, March.
    2. Jing Chen & Tao Li & Qilun Liu & Haiyan Jiao & Wenjun Yang & Xiaoxia Liu & Zhenghao Huo, 2014. "Clinical and Prognostic Significance of HIF-1α, PTEN, CD44v6, and Survivin for Gastric Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-15, March.
    3. Diandian Li & Yi Liu & Bo Wang, 2020. "Single versus bilateral lung transplantation in idiopathic pulmonary fibrosis: A systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 15(5), pages 1-12, May.

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