Abstract:Background and Aims: In recent years, an increasing number of researches have reported the relationship between the low expression of liver kinase B1 (LKB1) and the poor prognosis in cancer patients. However, a very few studies have reported opposite results, and some studies have shown that in addition to its anti-cancer effect, LKB1 also has a cancer-promoting effect. In the pathogenesis process of liver cancer, cancer cells may obtain genetic changes and induce cancer cell survival by activating the LKB1/AMPK pathway, such as Ras mutation or Skp2 overexpression. This study was conducted to further determine the relationship between low-expressing LKB1 and poor prognosis in cancer patients.
Methods: Literature searches were performed in Pubmed, Embase, and Cochrane Library databases by using relevant search terms. After literature screening according to the inclusion and exclusion criteria, data extraction and quality assessment were performed. The the relationship between LKB1 expression and prognosis of cancer patients were evaluated by Meta-analysis, the source of statistical heterogeneity was determined by subgroup analysis, and the influence of each individual study on the overall results was detected by sensitivity analysis.
Results: A total of 23 studies with 4 357 patients were finally. The NOS scores for all included studies ranged from 5 to 8, with a median score of 6.65. Among the studies, 22 reported the overall survival (OS), and the results showed that low LKB1 expression was associated with the unfavorable prognosis of the cancer patients (pooled HR=1.94, 95% CI=1.55–2.43, P<0.001); 12 studies reported the disease-free survival (DFS)/progression-free survival (PFS)/relapse-free survival (RFS), and the results showed that low LKB1 expression was associated with poor DFS/PFS/RFS of the cancer patients (pooled HR=1.53, 95% CI=1.08–2.17, P=0.017). The results of further subgroup analysis revealed that the risk or protective factors were the main source of heterogeneity. Finally, the results of the sensitivity analysis excluded the influence of each individual study on the overall results.
Conclusion: Although a very few studies have reported the pro-cancer effect of LKB1 in tumors, and the increased LKB1 expression may promote cancer development, this study confirms that low LKB1 expression is significantly associated with poor prognosis in patients with different types of cancers.