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GALNT2/14 过表达与预后和甲基化相关:肺腺癌的潜在治疗靶点。

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

机构信息

Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China.

Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China.

出版信息

Gene. 2021 Jul 20;790:145689. doi: 10.1016/j.gene.2021.145689. Epub 2021 May 5.

Abstract

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.

摘要

目的

GALNT2/14 是糖基转移酶蛋白家族的成员,它在高尔基体内启动肽的粘蛋白型 O-糖基化。然而,GALNT2/14 与肺腺癌(LUAD)疾病预后和甲基化的相关性尚不清楚。因此,我们试图确定其在 LUAD 中的潜在价值。

方法

使用公开可用的数据集分析 GALNT2/14 的表达。评估 GALNT2/14 与疾病预后的相关性。此外,还使用基因集富集分析(GSEA)和单样本 GSEA(ssGSEA)来探索 GALNT2/14 的潜在生物学功能。通过 cBioPortal 分析 GALNT2/14 的拷贝数变异与甲基化水平及其 mRNA 表达之间的相关性。最后,我们通过 MethSurv 在 LUAD 中探索了 GALNT2/14 甲基化水平的预后价值。

结果

与正常组织相比,LUAD 肿瘤组织中 GALNT2/14 的表达水平较高(P<0.001)。多变量分析表明,高 GALNT2/14 表达既是一个独立的预后因素。GSEA 发现,GALNT2/14 的表达与甲基化、基因沉默和细胞分裂有关,而免疫分析表明,GALNT2/14 的表达与 PD-L1 的表达水平呈正相关。最后,GALNT2/14 的甲基化水平与 GALNT2/14 的表达水平呈负相关(R=-0.26 和-0.36,P<0.001),GALNT2/14 低甲基化的患者总生存期比高甲基化的患者差(P<0.05)。

结论

本研究表明,LUAD 中 GALNT2/14 的过表达可作为预后不良的生物标志物。GALNT2/14 的生物学功能可能与甲基化、基因沉默、肿瘤发生和细胞分裂有关。这些发现有助于阐明 GALNT2/14 在肿瘤发生中的作用,并为 LUAD 的治疗和预后提供更多的见解。

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