Augmented expression of Ki-67 is correlated with clinicopathological characteristics and prognosis for lung cancer patients: an up-dated systematic review and meta-analysis with 108 studies and 14,732 patients

Respir Res. 2018 Aug 13;19(1):150. doi: 10.1186/s12931-018-0843-7.

Abstract

Background: Lung cancer ranks as the leading cause of cancer-related deaths worldwide and we performed this meta-analysis to investigate eligible studies and determine the prognostic effect of Ki-67.

Methods: In total, 108 studies in 95 articles with 14,732 patients were found to be eligible, of which 96 studies reported on overall survival (OS) and 19 studies reported on disease-free survival (DFS) with relation to Ki-67 expression in lung cancer patients.

Results: The pooled hazard ratio (HR) indicated that a high Ki-67 level could be a valuable prognostic factor for lung cancer (HR = 1.122 for OS, P < 0.001 and HR = 1.894 for DFS, P < 0.001). Subsequently, the results revealed that a high Ki-67 level was significantly associated with clinical parameters of lung cancer including age (odd ratio, OR = 1.246 for older patients, P = 0.018), gender (OR = 1.874 for males, P < 0.001) and smoking status (OR = 3.087 for smokers, P < 0.001). Additionally, significant positive correlations were found between Ki-67 overexpression and poorer differentiation (OR = 1.993, P = 0.003), larger tumor size (OR = 1.436, P = 0.003), and higher pathologic stages (OR = 1.867 for III-IV, P < 0.001). Furthermore, high expression of Ki-67 was found to be a valuable predictive factor for lymph node metastasis positive (OR = 1.653, P < 0.001) and advanced TNM stages (OR = 1.497 for stage III-IV, P = 0.024). Finally, no publication bias was detected in any of the analyses.

Conclusions: This study highlights that the high expression of Ki-67 is clinically relevant in terms of the prognostic and clinicopathological characteristics for lung cancer. Nevertheless, more prospective well-designed studies are warranted to validate these findings.

Keywords: Clinicopathological characteristics; Ki-67; Lung cancer; Meta-analysis; Prognosis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ki-67 Antigen / biosynthesis*
  • Ki-67 Antigen / genetics
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism*
  • Prognosis
  • Prospective Studies

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen