GALNT2/14 overexpression correlate with prognosis and methylation: potential therapeutic targets for lung adenocarcinoma

May 8, 2021Gene

Higher GALNT2 and GALNT14 levels linked to lung adenocarcinoma outcomes and DNA methylation, suggesting possible treatment targets

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Abstract

GALNT2/14 were highly expressed in lung adenocarcinoma (LUAD) tumor tissue compared to normal tissue (P < 0.001).

High expressions of GALNT2/14 were identified as independent prognostic factors in LUAD.
Gene set enrichment analysis indicated that GALNT2/14 expressions are associated with methylation, gene silencing, and cell division.
A positive correlation was observed between GALNT2/14 expressions and PD-L1 expression levels.
The methylation levels of GALNT2/14 negatively correlated with their mRNA expressions (R = -0.26 and -0.36, P < 0.001).
Patients with GALNT2/14 hypomethylation had worse overall survival compared to those with high methylation (P < 0.05).

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OBJECTIVE: GALNT2/14 are members of the glycosyltransferase protein family, which initiate mucin-type O-glycosylation of peptides in the Golgi apparatus. However, the correlation between GALNT2/14 and disease prognosis and methylation in lung adenocarcinoma (LUAD) remains unclear. Thus, we sought to identify their potential values in LUAD.

METHODS: GALNT2/14 expressions were analyzed using publicly-available datasets. The association between GALNT2/14 and disease prognosis was evaluated. In addition, gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to explore the potential biological functions of GALNT2/14. The correlation between the copy number variations and methylation level of GALNT2/14 and their mRNA expressions was analyzed via cBioPortal. Finally, we explored the prognostic value of the GALNT2/14 methylation levels by MethSurv in LUAD.

RESULTS: GALNT2/14 were highly expressed in LUAD tumor tissue than normal tissue (P < 0.001). Multivariate analysis showed that high GALNT2/14 expressions were both an independent prognostic factor. GSEA found that GALNT2/14 expressions were associated with the methylation, gene silencing, and cell division, whereas immune analysis showed that GALNT2/14 expressions positively correlated with the expression level of PD-L1. Finally, the methylation levels of GALNT2/14 negatively correlated with the GALNT2/14 expressions (R = -0.26 and -0.36, P < 0.001, respectively), and patients with GALNT2/14 hypomethylation had worse overall survival than patients with high methylation (P < 0.05).

CONCLUSIONS: This study demonstrated that the overexpression of GALNT2/14 in LUAD can serve as biomarkers for poor prognosis. The biological functions of GALNT2/14 are potentially related to methylation, gene silencing, tumorigenesis, and cell division. These findings help elucidate the role of GALNT2/14 in tumorigenesis and provide additional insight for therapy and prognosis of LUAD.

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GALNT2/14 overexpression correlate with prognosis and methylation: potential therapeutic targets for lung adenocarcinoma

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