AADAC 基因表达对 Borrmann Ⅲ型进展期胃癌患者预后的影响。
Impact of AADAC gene expression on prognosis in patients with Borrmann type III advanced gastric cancer.
机构信息
Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, 150081, China.
Department of Pathology, Harbin Medical University, Harbin, China.
出版信息
BMC Cancer. 2022 Jun 9;22(1):635. doi: 10.1186/s12885-022-09594-1.
BACKGROUND
The prognosis of Borrmann type III advanced gastric cancer (AGC) is known to vary significantly among patients. This study aimed to determine which differentially expressed genes (DEGs) are directly related to the survival time of Borrmann type III AGC patients and to construct a prognostic model.
METHODS
We selected 25 patients with Borrmann type III AGC who underwent radical gastrectomy. According to the difference in overall survival (OS), the patients were divided into group A (OS<1 year, n=11) and group B (OS>3 years, n=14). DEGs related to survival time in patients with Borrmann type III AGC were determined by mRNA sequencing. The prognosis and functional differences of DEGs in different populations were determined by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The expression of mRNA and protein in cell lines was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemical (IHC) staining was used to detect protein expression in the paraffin-embedded tissues of 152 patients with Borrmann type III AGC who underwent radical gastrectomy. After survival analysis, nomograms were constructed to predict the prognosis of patients with Borrmann type III AGC.
RESULTS
Arylacetamide deacetylase (AADAC) is a survival-related DEG in patients with Borrmann type III AGC. The higher the expression level of its mRNA and protein is, the better the prognosis of patients. Bioinformatics analysis found that AADAC showed significant differences in prognosis and function in European and American populations and Asian populations. In addition, the mRNA and protein expression levels of AADAC were high in differentiated gastric cancer (GC) cells. We also found that AADAC was an independent prognostic factor for patients with Borrmann type III AGC, and its high expression was significantly correlated with better OS and disease-free survival (DFS). Nomogram models of AADAC expression level combined with clinicopathological features can be used to predict the OS and DFS of Borrmann type III AGC.
CONCLUSION
AADAC can be used as a biomarker to predict the prognosis of Borrmann type III AGC and has the potential to become a new therapeutic target for GC.
背景
Borrmann Ⅲ型进展期胃癌（AGC）的预后在患者之间差异显著。本研究旨在确定哪些差异表达基因（DEGs）与 Borrmann Ⅲ型 AGC 患者的生存时间直接相关，并构建预后模型。
方法
我们选择了 25 例接受根治性胃切除术的 Borrmann Ⅲ型 AGC 患者。根据总生存期（OS）的差异，将患者分为 A 组（OS<1 年，n=11）和 B 组（OS>3 年，n=14）。通过 mRNA 测序确定与 Borrmann Ⅲ型 AGC 患者生存时间相关的 DEGs。通过 The Cancer Genome Atlas（TCGA）和 Gene Expression Omnibus（GEO）公共数据库确定 DEGs 在不同人群中的预后和功能差异。通过定量实时逆转录聚合酶链反应（qRT-PCR）和 Western blot（WB）检测细胞系中 mRNA 和蛋白的表达。免疫组织化学（IHC）染色检测 152 例接受根治性胃切除术的 Borrmann Ⅲ型 AGC 患者石蜡包埋组织中的蛋白表达。生存分析后，构建列线图预测 Borrmann Ⅲ型 AGC 患者的预后。
结果
芳基乙酰胺脱乙酰酶（AADAC）是 Borrmann Ⅲ型 AGC 患者的生存相关 DEG。其 mRNA 和蛋白表达水平越高，患者预后越好。生物信息学分析发现，AADAC 在欧美人群和亚洲人群中的预后和功能存在显著差异。此外，AADAC 在分化型胃癌（GC）细胞中的 mRNA 和蛋白表达水平较高。我们还发现，AADAC 是 Borrmann Ⅲ型 AGC 患者的独立预后因素，其高表达与更好的 OS 和无病生存期（DFS）显著相关。基于 AADAC 表达水平与临床病理特征相结合的列线图模型可用于预测 Borrmann Ⅲ型 AGC 的 OS 和 DFS。
结论
AADAC 可作为预测 Borrmann Ⅲ型 AGC 预后的生物标志物，并有成为 GC 新治疗靶点的潜力。
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