Yang Qiuxing, Cai Bo, Zhu Shudong, Tai Guomei, Shen Aiguo
Cancer Research Center Nantong, Nantong Tumor Hospital, Affiliated Tumor Hospital of Nantong University, Nantong, China.
Nantong Center for Disease Control and Prevention Institute of Chronic Noncommunicable Diseases Prevention and Control, Nantong, China.
J Cancer. 2024 Aug 19;15(16):5351-5366. doi: 10.7150/jca.88767. eCollection 2024.
Esophageal squamous cell carcinoma (ESCC), one of the most aggressive gastrointestinal malignancies, remains an enormous challenge in terms of medical treatment and prognostic improvement. Based on the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases in R language, the myeloid-associated differentiation marker (MYADM) was confirmed using bioinformatics analysis and experimental verification. MYADM is upregulated in multiple cancer types; however, the oncogenic mechanism by which MYADM promotes ESCC remains largely unknown. In the present study, we used weighted gene coexpression network analysis to filter four hub genes (AKAP12, ITGA1, JAM2, and MYADM) in GSE45670 and GSE23400 that are related to the malignant progression of ESCC. Transcription factors and target miRNAs of the hub genes were predicted using the TarBase and JASPRAR databases, respectively, and a regulatory network was established. MYADM was selected based on the analysis of expression differences and prognostic value in ESCC. Next, we confirmed the level of MYADM in ESCC samples using immunohistochemistry of the tissue microarray. The molecular mechanisms of MYADM were further elucidated by experimental analyses, including Transwell assays, wound healing assays, and CCK8. The correlation between MYADM levels and the clinical data of patients with ESCC was confirmed, including tumor differentiation, the node and metastasis stage, T stage, lymphatic metastasis, and postoperative distant metastasis. MYADM was significantly upregulated in ESCC and positively correlated with overall survival. MYADM induced cell proliferation, migration, invasion, and wound healing via the epithelial to mesenchymal transition (EMT) pathway in multiple experiments. Moreover, our results supported the hypothesis that MYADM promotes EMT during paclitaxel resistance. MYADM is closely correlated with ESCC progression, metastasis, and paclitaxel resistance and could be regarded as a novel biomarker and therapeutic target for ESCC patients.
食管鳞状细胞癌（ESCC）是最具侵袭性的胃肠道恶性肿瘤之一，在医学治疗和改善预后方面仍然是一个巨大的挑战。基于R语言中的基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库，通过生物信息学分析和实验验证确定了髓系相关分化标志物（MYADM）。MYADM在多种癌症类型中上调；然而，MYADM促进ESCC的致癌机制在很大程度上仍不清楚。在本研究中，我们使用加权基因共表达网络分析在GSE45670和GSE23400中筛选出与ESCC恶性进展相关的四个枢纽基因（AKAP12、ITGA1、JAM2和MYADM）。分别使用TarBase和JASPRAR数据库预测枢纽基因的转录因子和靶miRNA，并建立调控网络。基于对ESCC中表达差异和预后价值的分析选择了MYADM。接下来，我们通过组织芯片的免疫组织化学证实了ESCC样本中MYADM的水平。通过Transwell实验、伤口愈合实验和CCK8等实验分析进一步阐明了MYADM的分子机制。证实了MYADM水平与ESCC患者临床数据之间的相关性，包括肿瘤分化、淋巴结和转移分期、T分期、淋巴转移和术后远处转移。MYADM在ESCC中显著上调，与总生存期呈正相关。在多个实验中，MYADM通过上皮-间质转化（EMT）途径诱导细胞增殖、迁移、侵袭和伤口愈合。此外，我们的结果支持了MYADM在紫杉醇耐药期间促进EMT的假设。MYADM与ESCC的进展、转移和紫杉醇耐药密切相关，可被视为ESCC患者的一种新型生物标志物和治疗靶点。
