The Prognostic Value of Decreased LKB1 in Solid Tumors: A Meta-Analysis

Jian Xiao; Yong Zou; Xi Chen; Ying Gao; Mingxuan Xie; Xiaoxiao Lu; Wei Li; Bixiu He; Shuya He; Shaojin You; Qiong Chen

doi:10.1371/journal.pone.0152674

The Prognostic Value of Decreased LKB1 in Solid Tumors: A Meta-Analysis

PLoS One. 2016 Apr 1;11(4):e0152674. doi: 10.1371/journal.pone.0152674. eCollection 2016.

Authors

Jian Xiao¹, Yong Zou¹, Xi Chen², Ying Gao¹, Mingxuan Xie¹, Xiaoxiao Lu¹, Wei Li¹, Bixiu He¹, Shuya He³, Shaojin You⁴, Qiong Chen¹

Affiliations

¹ Department of Geriatrics, Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, China.
² Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, China.
³ Department of Biochemistry and Biology, University of South China, Hengyang, China.
⁴ Laboratory of Cancer Experimental Therapy, Atlanta Research & Educational Foundation (151F), Atlanta VA Medical Center, Decatur, GA, United States of America.

Abstract

Background: Liver kinase B1 (LKB1) is a protein kinase that regulates the growth, integrity and polarity of mammalian cells. Recent studies have reported the prognostic value of decreased LKB1 expression in different tumors. However, the results of these studies remain controversial. Therefore, this meta-analysis was performed to more accurately estimate the role of decreased LKB1 in the prognostication of human solid tumors.

Methods: A systematic literature search in the electronic databases PubMed, Embase, Web of Science and CNKI (updated to October 15, 2015) was performed to identify eligible studies. The overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and clinicopathological features data were collected from these studies. The hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and pooled with a random-effects models using Stata12.0 software.

Results: A total of 14 studies covering 1915 patients with solid tumors were included in this meta-analysis. Decreased LKB1 was associated with poorer OS in both the univariate (HR: 1.86, 95%CI: 1.42-2.42, P<0.001) and multivariate (HR: 1.55, 95%CI: 1.09-2.21, P = 0.015) analyses. A subgroup analysis revealed that the associations between decreased LKB1 and poor OS were significant within the Asian region (HR 2.18, 95%CI: 1.66-2.86, P<0.001) and obvious for lung cancer (HR: 2.16, 95%CI: 1.47-3.18, P<0.001). However, the articles that involved analyses of both RFS and DFS numbered only 3, and no statistically significant correlations of decreased LKB1 with RFS or DFS were observed in this study. Additionally, the pooled odds ratios (ORs) indicated that decreased LKB1 was associated with larger tumor size (OR: 1.60, 95%CI: 1.09-2.36, P = 0.017), lymph node metastasis (OR: 2.41, 95%CI: 1.53-3.78, P<0.001) and a higher TNM stage (OR: 3.35, 95%CI: 2.20-5.09, P<0.001).

Conclusion: These results suggest that decreased LKB1 expression in patients with solid tumors might be related to poor prognosis and serve as a potential predictive marker of poor clinicopathological prognostic factors. Additional studies are required to verify the clinical utility of decreased LKB1 in solid tumors.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinase Kinases
Humans
Neoplasms / metabolism*
Prognosis
Protein Serine-Threonine Kinases / metabolism*

Substances

Protein Serine-Threonine Kinases
STK11 protein, human
AMP-Activated Protein Kinase Kinases

Grants and funding

This work was supported by funding from the National Natural Science Foundation of China (81572284). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.