基于TCGA数据，A激酶锚定蛋白5低表达预示非黏液性胃腺癌预后不良。
Low expression of A-kinase anchor protein 5 predicts poor prognosis in non-mucin producing stomach adenocarcinoma based on TCGA data.
作者信息
Zhong Zishao, Ye Zhenhao, He Guihua, Zhang Wang, Wang Jing, Huang Suiping
机构信息
Gastroenterology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
Gastroenterology Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China.
出版信息
Ann Transl Med. 2020 Feb;8(4):115. doi: 10.21037/atm.2019.12.98.
BACKGROUND
In the past, there were not a lot of studies on how A-kinase anchor protein 5 (AKAP5) involving in the pathogenesis and prognosis of non-mucin producing stomach adenocarcinoma (NMSA). Therefore, we studied the relationship between AKAP5 and the prognosis of NMSA and its possible mechanisms using publicly available data from The Cancer Genome Atlas (TCGA).
METHODS
RNA high-throughput sequencing and clinicopathologic data of NMSA were downloaded from the TCGA. Clinical pathologic features associated with AKAP5 expression were analyzed using the chi-square and Fisher exact tests. The relationship between the overall survival (OS) and AKAP5 expression was analyzed by the Kaplan-Meier method and the Cox regression analysis. GSEA analysis was performed using the TCGA dataset.
RESULTS
Our results indicated that the AKAP5 expression was increased in NMSA (all tumor . adjacent mucosa). Also, histologic grade, clinical stage, N classification, and survival status were significantly correlated with AKAP5 expression. Kaplan-Meier curves showed that low AKAP5 expression was associated with a poor OS among the NMSA patients (P=5.003e-05), and in the clinical stage III and IV (P=4.646e-05), TNM stage T3 (P=0.016), T4 (P=0.001), N2 (P=0.012), N3 (P=0.003), M0 (P=3.911e-05), and histological grade G3 (P=1.658e-04) subgroups. Cox regression analysis showed that reduced AKAP5 expression in NMSA is associated with age (HR =1.03, P=0.007), stage (HR =1.84 for stage I, II . stage III, IV, P=0.002) and M classification (HR =1.8 for M0 . M1, P=0.010). Gene sets related to cholesterol homeostasis, glycolysis, estrogen response late, adipogenesis, estrogen response early, notch signaling, and peroxisome were differentially enriched with the low AKAP5 expression phenotype.
CONCLUSIONS
Low expression of AKAP5 may be a potential molecular marker for predicting poor prognosis of NMSA. Besides, cholesterol homeostasis, glycolysis, estrogen response, adipogenesis, notch signaling, and peroxisome may be the key pathways regulated by AKAP5 in NMSA. It also suggested that AKAP5 might potentially have biological functions in the development of stomach adenocarcinoma.
背景
过去，关于A激酶锚定蛋白5（AKAP5）如何参与非黏液性胃腺癌（NMSA）的发病机制和预后的研究并不多。因此，我们利用来自癌症基因组图谱（TCGA）的公开可用数据，研究了AKAP5与NMSA预后之间的关系及其可能机制。
方法
从TCGA下载NMSA的RNA高通量测序和临床病理数据。使用卡方检验和Fisher精确检验分析与AKAP5表达相关的临床病理特征。采用Kaplan-Meier法和Cox回归分析分析总生存期（OS）与AKAP5表达之间的关系。使用TCGA数据集进行基因集富集分析（GSEA）。
结果
我们的结果表明，NMSA中AKAP5表达增加（所有肿瘤.相邻黏膜）。此外，组织学分级、临床分期、N分类和生存状态与AKAP5表达显著相关。Kaplan-Meier曲线显示，NMSA患者中低AKAP5表达与较差的OS相关（P = 5.003e-05），在临床III期和IV期（P = 4.646e-05）、TNM分期T3（P = 0.016）、T4（P = 0.001）、N2（P = 0.012）、N3（P = 0.003）、M0（P = 3.911e-05）和组织学分级G3（P = 1.658e-04）亚组中也是如此。Cox回归分析表明，NMSA中AKAP5表达降低与年龄（HR = 1.03，P = 0.007）、分期（I、II期与III、IV期相比，HR = 1.84，P = 0.002）和M分类（M0与M1相比，HR = 1.8，P = 0.010）有关。与胆固醇稳态、糖酵解、雌激素晚期反应、脂肪生成、雌激素早期反应、Notch信号和过氧化物酶体相关的基因集在低AKAP5表达表型中差异富集。
结论
AKAP5低表达可能是预测NMSA预后不良的潜在分子标志物。此外，胆固醇稳态、糖酵解、雌激素反应、脂肪生成、Notch信号和过氧化物酶体可能是AKAP5在NMSA中调控的关键途径。这也表明AKAP5在胃腺癌的发生发展中可能具有生物学功能。
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