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

Abstract

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.

Phe354Leu polymorphism of the liver kinase B1 gene as a prognostic factor in adult egyptian patients with acute myeloid leukemia

“…Furthermore, the loss of LKB1 was associated with an increased risk of recurrence and death in patients with resected colon cancer [ 42 ]. Patients with low LKB1 expression had significantly worse tumor differentiation, larger tumors, early lymph node metastasis, advanced TNM stage, and poor treatment response [ 45 ].…”

STK11 and KEAP1 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value among Hispanics (STRIKE registry-CLICaP)

“…A marginal association was found between STK11 Mut or KEAP1 Mut (p = 0.079) and the novo brain metastasis. Current data shows that STK11 mutations induce tumor microenvironment changes that promote angiogenesis and recruit an immunosuppressive cell infiltrate [31,32] Moreover, STK11 alterations have been associated with poor tumor differentiation, increased invasive capacity, early lymph node metastasis, and advanced TNM stage [33]. All the molecular processes facilitated by STK11 mutations increase the invasiveness of lung cancer cells and promote colonization of distant sites, which could explain the early development of brain metastasis found in association with mutation in STK11.…”

LKB1 expression and the prognosis of lung cancer

“…[37] A previous study has provided certain information regarding the prognostic value of LKB1 in patients with solid tumours. [38,39] However, no meta-analysis have been performed to evaluate the prognostic value of LKB1 expression in lung cancer. This meta-analysis is aimed to investigate the effect of LKB1 expression on the prognosis and clinicopathological characteristics in lung cancer.…”

“…Furthermore, the data have indicated that LKB1 mutation in NSCLC conferred enhanced radio sensitization in combination with trametinib, suggesting LKB1 mutation as a biomarker for patient's trametinib and radiotherapy combination therapy [37] . A previous study has provided certain information regarding the prognostic value of LKB1 in patients with solid tumours [38,39] . However, no meta-analysis have been performed to evaluate the prognostic value of LKB1 expression in lung cancer.…”