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糖酵解相关基因分析表明 DEPDC1 通过 WNT/β-连环蛋白信号通路促进口腔鳞状细胞癌的恶性进展。

Glycolysis-Related Gene Analyses Indicate That DEPDC1 Promotes the Malignant Progression of Oral Squamous Cell Carcinoma via the WNT/β-Catenin Signaling Pathway.

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610044, China.

Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610044, China.

出版信息

Int J Mol Sci. 2023 Jan 19;24(3):1992. doi: 10.3390/ijms24031992.

Abstract

Increasing evidence suggests that aerobic glycolysis is related to the progression of oral squamous cell carcinoma (OSCC). Hence, we focused on glycolysis-related gene sets to screen for potential therapeutic targets for OSCC. The expression profiles of OSCC samples and normal controls were obtained from The Cancer Genome Atlas (TCGA). Then, the differentially expressed gene sets were selected from the official GSEA website following extraction of the differentially expressed core genes (DECGs). Subsequently, we tried to build a risk model on the basis of DECGs to predict the prognosis of OSCC patients via Cox regression analysis. Furthermore, crucial glycolysis-related genes were selected to explore their biological roles in OSCC. Two active glycolysis-related pathways were acquired and 66 DECGs were identified. Univariate Cox regression analysis showed that six genes, including HMMR, STC2, DDIT4, DEPDC1, SLC16A3, and AURKA, might be potential prognostic factors. Subsequently, a risk formula consisting of DEPDC1, DDIT4, and SLC16A3 was established on basis of the six molecules. Furthermore, DEPDC1 was proven to be related to advanced stage cancer and lymph node metastasis. Moreover, functional experiments suggested that DEPDC1 promoted the aerobic glycolysis, migration, and invasion of OSCC via the WNT/β-catenin pathway. The risk score according to glycolysis-related gene expression might be an independent prognostic factor in OSCC. In addition, DEPDC1 was identified as playing a carcinogenic role in OSCC progression, suggesting that DEPDC1 might be a novel biomarker and therapeutic target for OSCC.

摘要

越来越多的证据表明,有氧糖酵解与口腔鳞状细胞癌(OSCC)的进展有关。因此,我们专注于糖酵解相关基因集,以筛选 OSCC 的潜在治疗靶点。OSCC 样本和正常对照的表达谱从癌症基因组图谱(TCGA)中获得。然后,从官方 GSEA 网站提取差异表达核心基因(DECGs)后,选择差异表达基因集。随后,我们尝试基于 DECGs 构建风险模型,通过 Cox 回归分析预测 OSCC 患者的预后。此外,选择关键的糖酵解相关基因来探索它们在 OSCC 中的生物学作用。获得了两条活跃的糖酵解相关途径和 66 个 DECGs。单变量 Cox 回归分析表明,HMMR、STC2、DDIT4、DEPDC1、SLC16A3 和 AURKA 这 6 个基因可能是潜在的预后因素。随后,基于这 6 个分子建立了一个由 DEPDC1、DDIT4 和 SLC16A3 组成的风险公式。此外,DEPDC1 被证明与晚期癌症和淋巴结转移有关。此外,功能实验表明,DEPDC1 通过 WNT/β-catenin 通路促进 OSCC 的有氧糖酵解、迁移和侵袭。基于糖酵解相关基因表达的风险评分可能是 OSCC 的独立预后因素。此外,DEPDC1 被确定在 OSCC 进展中发挥致癌作用,表明 DEPDC1 可能是 OSCC 的一种新的生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1740/9916831/ec5a3f37c696/ijms-24-01992-g001.jpg

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