Liu Xi, Chen Lei, Zhang Tao
1 Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, People's Republic of China.
Cancer Control. 2018 Jan-Mar;25(1):1073274818778001. doi: 10.1177/1073274818778001.
Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years' survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (-1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = -0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.
高尔基体膜蛋白1（GOLM1）是一种高尔基体潴泡的跨膜糖蛋白，与多种类型癌症的发生有关。在本研究中，我们利用基因表达综合数据库（Gene Expression Omnibus）和癌症基因组图谱（The Cancer Genome Atlas）的数据，比较了GOLM1在肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）中的表达情况，并研究了其在这两种非小细胞肺癌（NSCLC）亚型中的总生存期（OS）和无复发生存期（RFS）的预后价值。结果显示，与正常对照相比，GOLM1在LUAD和LUSC组织中均显著上调。然而，GOLM1在LUAD组织中的表达高于LUSC组织。更重要的是，利用502例LUAD患者和494例LUSC患者超过10年的生存数据，我们发现GOLM1高表达与LUAD患者不良的OS和RFS相关，但与LUSC患者无关。随后的单因素和多因素分析证实，GOLM1表达增加是LUAD患者OS不良（风险比[HR]：1.30，95%置信区间[CI]：1.11 - 1.54，P = 0.002）和RFS不良（HR：1.37，95% CI：1.14 - 1.64，P = 0.001）的独立预后指标。在511例LUAD病例中，248例（48.5%）存在杂合性缺失（-1），而511例LUAD病例中有28例（5.5%）存在低水平拷贝数增加（+1）。此外，我们还发现1个CpG位点（chr9: 88,694,942 - 88,694,944）的甲基化状态与GOLM1表达呈弱负相关（Pearson相关系数r = -0.25）。基于这些发现，我们推断GOLM1可能是LUAD中有价值的预后生物标志物，但在LUSC中并非如此。此外，DNA拷贝数改变和甲基化可能是LUAD中GOLM1失调的两个重要机制。
