Wang Li, Zhang Mingxin, Wang Jiansheng, Zhang Jia
Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Surgery, The Hospital of Chang'an University, Xi'an, Shaanxi, China.
J Cell Biochem. 2021 May 4;122(9):1062-71. doi: 10.1002/jcb.29927.
Mixed-type gastric adenocarcinoma (by Lauren Classification) has poor clinical outcomes with few targeted treatment options. The primary objective of this study was to find the prognostic factors, accurate treatment approaches, and effective postoperative adjuvant therapy strategies for patients with mixed-type gastric adenocarcinoma (GA). A microRNA sequencing data set and the corresponding clinical parameters of patients with gastric cancer were obtained from The Cancer Genome Atlas. Differentially expressed microRNAs (DEMs) of diffuse- and intestinal-type GA were, respectively, determined. Kaplan-Meier and log-rank tests were subsequently carried out to evaluate the prognostic relevance of each DEM. To study the common factors between diffuse- and intestinal-type GA, a pathway enrichment analysis was performed on the target genes of identified DEMs using the PANTHER database. After data preprocessing, we analyzed a total of 230 samples from 210 patients with GA. Eighty-six DEMs in diffuse-type GA samples and 59 DEMs in intestinal-type GA samples were, respectively, identified (p 2.0). The Kaplan-Meier survival method further screened out six prognosis-related DEMs for diffuse-type GA and seven prognosis-related DEMs for intestinal-type GA (p < 0.05). MiR-18a-5p was found to be the only common prognosis-related DEM between diffuse- and intestinal-type GA. The common signaling pathways further revealed that target genes of miR-18a-5p are involved in mixed-type GA progression. This study suggests that miR-18a-5p acts as a potential target for treatment, and common signal pathways provide a rich basis to seek reliable and effective molecular targets for the diagnosis, clinical treatment, and postoperative adjuvant therapy strategy of mixed-type GA.
混合型胃腺癌(根据劳伦分类法)临床预后较差,且几乎没有靶向治疗方案。本研究的主要目的是为混合型胃腺癌(GA)患者寻找预后因素、准确的治疗方法以及有效的术后辅助治疗策略。从癌症基因组图谱中获取了胃癌患者的一个微小RNA测序数据集及相应的临床参数。分别确定了弥漫型和肠型GA中差异表达的微小RNA(DEM)。随后进行了Kaplan-Meier和对数秩检验,以评估每个DEM的预后相关性。为了研究弥漫型和肠型GA之间的共同因素,使用PANTHER数据库对已识别DEM的靶基因进行了通路富集分析。经过数据预处理,我们共分析了来自210例GA患者的230个样本。分别在弥漫型GA样本中鉴定出86个DEM,在肠型GA样本中鉴定出59个DEM(p < 2.0)。Kaplan-Meier生存方法进一步筛选出弥漫型GA的6个与预后相关的DEM和肠型GA的7个与预后相关的DEM(p < 0.05)。发现miR-18a-5p是弥漫型和肠型GA之间唯一共同的与预后相关的DEM。共同的信号通路进一步揭示,miR-18a-5p的靶基因参与了混合型GA的进展。本研究表明,miR-18a-5p可作为潜在的治疗靶点,共同信号通路为寻找可靠有效的分子靶点以用于混合型GA的诊断、临床治疗及术后辅助治疗策略提供了丰富依据。