BMJ Open (Aug 2019)

Association between LKB1 expression and prognosis of patients with solid tumours: an updated systematic review and meta-analysis

  • Yun Hong Ren,
  • Feng Juan Zhao,
  • Han Yue Mo,
  • Rong Rong Jia,
  • Juan Tang,
  • Xin Hua Zhao,
  • Jue Ling Wei,
  • Rong Rui Huo,
  • Qiu Qin Li,
  • Xue Mei You

DOI
https://doi.org/10.1136/bmjopen-2018-027185
Journal volume & issue
Vol. 9, no. 8

Abstract

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ObjectivesLiver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question.DesignAn updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed.Data sourcesEligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases.Eligibility criteriaThe association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI.Data extraction and synthesisRelevant data were meta-analysed for OS, DFS, RFS and various clinical parameters.ResultsThe systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01).ConclusionLow LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.