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通过多种方法联合检测 CDH11 在口腔鳞状细胞癌中的表达特征和分子基础。

Expression signature and molecular basis of CDH11 in OSCC detected by a combination of multiple methods.

机构信息

Department of Oral and Maxillofacial Surgery, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China.

Department of Stomatology, People's hospital of Yongning District, Nanning, 530200, China.

出版信息

BMC Med Genomics. 2023 Apr 3;16(1):70. doi: 10.1186/s12920-023-01499-7.

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common malignancy in the oral cancer threatening human health and the survival rate of OSCC has not been effectively improved in recent decades, so more effective biomarkers for the targeted therapy of OSCC are needed. Moreover, the role of CDH11 in OSCC has not been intensively investigated. We here show that the CDH11 protein and mRNA expression levels in the OSCC tissues were all significantly higher than in the non-cancerous tissues using RT-qPCR and western blot. This study also revealed that patients with higher CDH11 levels showed a higher incidence of perineural invasion and lymph node metastasis. By using data available from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress databases, overexpressed CDH11 in OSCC that associated with patients'history of alcohol, negative Human Papilloma Virus (HPV) status, perineural invasion, infiltration of multiple immune cells, and Single-cell functional states including quiescence and angiogenesis, possessed an excellent discriminatory capability in the OSCC patients. Moreover, the majority of the biological processes or pathways were significantly clustered by co-expressed genes, including extracellular matrix organization, the epithelial to mesenchymal transition, carbon metabolism, and the PI3K-Akt signaling pathway, and the upstream transcriptional regulation mechanism of CDH11 in OSCC was showed on a transcription factor/miRNA-mRNA network with the online tool NetworkAnalyst. Finally, frequent mutation of CDH11 was observed on a mouse OSCC model through whole-genome sequencing. CDH11 might serve as a valuable biomarker in OSCC, as it was identified to be overexpressed in OSCC and related to its clinical progression.

摘要

口腔鳞状细胞癌(OSCC)是口腔癌中最常见的恶性肿瘤之一,威胁着人类健康,近几十年来 OSCC 的生存率并未得到有效提高,因此需要更有效的 OSCC 靶向治疗生物标志物。此外,CDH11 在 OSCC 中的作用尚未得到深入研究。我们通过 RT-qPCR 和 Western blot 显示 OSCC 组织中的 CDH11 蛋白和 mRNA 表达水平均明显高于非癌组织。本研究还表明,CDH11 水平较高的患者出现神经周围侵犯和淋巴结转移的发生率更高。通过使用来自癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)和 ArrayExpress 数据库的数据,我们发现 OSCC 中 CDH11 的过表达与患者的饮酒史、HPV 状态阴性、神经周围侵犯、多种免疫细胞浸润以及单细胞功能状态(包括静止和血管生成)有关,在 OSCC 患者中具有出色的区分能力。此外,大多数生物过程或途径通过共表达基因显著聚类,包括细胞外基质组织、上皮间质转化、碳代谢和 PI3K-Akt 信号通路,并且在线工具 NetworkAnalyst 显示了 CDH11 在 OSCC 中的转录因子/miRNA-mRNA 网络的上游转录调控机制。最后,通过全基因组测序在小鼠 OSCC 模型中观察到 CDH11 的频繁突变。CDH11 可能作为 OSCC 的有价值的生物标志物,因为它在 OSCC 中被鉴定为过表达,并与 OSCC 的临床进展有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4f/10069064/b6bd83bd7538/12920_2023_1499_Fig6_HTML.jpg

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