Low-level gastrokine 2 promoted progress of NSCLC and as a potential biomarker

Abstract

Background: Gastrokine 2 (GKN2) is significantly downregulated in non-small cell lung cancer (NSCLC) tissues than in normal tissues (NT), as assessed by mRNA microassay; however, the mechanism and clinical value of GKN2 is unknown in NSCLC.

Methods: A total of 60 NSCLC samples and corresponding NT samples were prospectively collected GKN2 expression in NSCLC tissues was estimated. Also, the expression level of GKN2 promoter methylation and correlation with clinical data in NSCLC patients from public databases were analyzed. Cytology experiments were also carried out.

Results: The GKN2 mRNA and protein expression level in NSCLC was significantly lower than that in the NT, and the GKN2 expression level in large tumors NSCLC was significantly lower than that in the small tumor group. Public data showed that expression of GKN2 in LUAD with P53 mutation group was lower than that of the P53 non-mutation group, and GKN2 promoter methylation level of LUAD was significantly higher than its NT and close to age and clinical stage. Cell migration, invasion, and proliferation ability of GKN2 overexpressed were lower in A549 and PC9 groups than those in GKN2 overexpressed A549 and PC9 negative control groups, while the percentage of apoptotic cells increased in the GKN2 overexpressed A549 and PC9 groups. The DNMT3B mRNA expression levels were higher in PC9 and A549 cells than BEAS-2B cells.

Conclusion: The overexpression of GKN2 significantly inhibited cell proliferation, migration, and invasion and promoted apoptosis. Low-level GKN2 promoted the progression of NSCLC via DNMT3B and is expected to be a biomarker for NSCLC.

Keywords: biomarker; gastrokine 2; methylation; non-small cell lung cancer.