GC is a global health problem, with one million new cases occurring annually worldwide. Despite improvements in treatment over the past decade, GC’s survival rate remains low [28]. The importance of early diagnosis and treatment has become increasingly prominent. Rapid advances in biotechnology have improved our understanding of the molecules and specific biomarkers associated with cancer, thus facilitating new-drug discovery and the application of novel diagnostic methods [29]. Recently, many studies have explored the relationship between LKB1 expression and clinicopathological parameters; however, the results have been inconsistent. Therefore, this meta-analysis was conducted to explore the homogeneity of patient baseline data. Moreover, this systematic review and meta-analysis investigated the relationship between LKB1 expression and the clinicopathological parameters of GC and found LKB1 expression to be (1) independent of sex and age; (2) significantly correlated with tumor size, degree of differentiation, depth of invasion, lymph node metastasis, and TNM stage; (3) significantly correlated with OS at one, three, and five years; and a negative factor for poor prognosis. Overall, our findings indicate that LKB1 expression is a potential biomarker for predicting the survival prognosis of patients with GC.
While LKB1 expression has been found to be associated with GC [20], as regards the relationship between baseline data and LKB1 expression in patients with GC, several subsequent studies have revealed that LKB1 expression is not related to the sex and age of patients with GC. For example, studies conducted by Li et al. and Hu et al. demonstrated that high LKB1 expression is not related to the sex and age of patients with GC [14, 23]. Our meta-analysis found no difference in LKB1 expression according to sex (P = 0.068) and age (P = 0.108) among patients with GC.
Many conflicting results exist in the literature regarding LKB1 expression and clinicopathological parameters in patients with GC. First, Ma et al. suggested that high LKB1 expression is correlated with GC tumor size [15]. However, a study conducted by Zhao et al. revealed no statistically significant differences among the parameters [27]. Our meta-analysis results (P = 0.008) indicated that high LKB1 expression is associated with GC tumor size and is a negative factor for GC growth. Second, data from certain studies indicate a relationship between LKB1 expression and the degree of GC differentiation [21, 26, 27]. Nonetheless, Li et al. believe that LKB1 expression is not associated with differentiation [23]. Our meta-analysis revealed that high LKB1 expression is a protective factor against a low degree of GC differentiation (P < 0.001). Third, data have shown that high LKB1 expression is related to the depth of GC invasion [3, 14, 15, 23]. Therefore, a previous notion that high LKB1 expression is unrelated to the depth of GC invasion has since been rejected [22]. The data (P < 0.001) collected in our meta-analysis indicate that high LKB1 expression is a negative factor for the depth of invasion. Fourth, certain researchers believe that high LKB1 expression is related to lymph node metastasis in GC [3, 14, 15, 22, 23]. Nevertheless, others have suggested that high LKB1 expression is unrelated to lymph node metastasis in GC [21, 27]. According to our results (P < 0.001), it could be deduced that high LKB1 expression is a negative factor for lymph node metastasis in GC. Fifth, some studies have concluded that LKB1 expression is linked to TNM staging [14, 15, 22, 23, 27], whereas others have suggested that LKB1 expression is not related to the GC TNM stage [20]. The results of our meta-analysis indicate (P = 0.006) that high LKB1 expression is a negative factor for pathological TNM staging. In summary, LKB1 expression is associated with GC invasion and metastasis, and high LKB1 expression is a negative factor for GC invasion and metastasis.
Some studies have suggested that high LKB1 expression enhances OS. For example, a study conducted by Li et al. showed that high LKB1 expression is a favorable factor for OS (P < 0.001) and an independent prognostic marker in GC [23]. Our meta-analysis concluded that high LKB1 expression is significantly associated with favorable one-, three-, and five-year OS rates. In addition, LKB1 expression may be an important marker for predicting GC prognosis. Some studies have suggested that LKB1 loss promotes tumor proliferation by altering the NKX2-1/p53 pathway [30] and that loss of the LKB1–AMPK signaling pathway is associated with prognosis in patients undergoing advanced non-small cell lung cancer chemotherapy [31]. However, the mechanism by which LKB1 affects GC prognosis warrants further study.
Limitations
Certain limitations should be considered when interpreting this study’s results. First, the literature selected for this meta-analysis was geographically limited, predominantly originating from East Asia. Second, the included studies were relatively limited in terms of sample size and the total number of people involved in the meta-analysis. Third, the language types included in the study were restricted to Chinese and English, and articles published in other languages were excluded. Fourth, not all specific 95% CI values were directly extracted from the studies. Survival data were extracted from Kaplan–Meier curves. Fifth, avoiding study heterogeneity and other biases proved challenging. Therefore, further research is required to evaluate the relationship between LKB1 expression and the clinicopathological features and prognosis of patients with GC.