Zhou Lijie, Li Hongyu, Cai Hongshi, Liu Wenhui, Pan Enjiu, Yu Dongsheng, He Shuai
Department of Stomatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
Front Oncol. 2022 Mar 1;12:809589. doi: 10.3389/fonc.2022.809589. eCollection 2022.
The strong invasive and metastatic abilities of oral squamous cell carcinoma (OSCC) cells in the early stage are the main reason for its poor prognosis. The early diagnosis and treatment of OSCC may reduce the metastasis rate and improve the survival rate. The aim of this study was to explore candidate biomarkers related to the prognosis and progression of OSCC. We performed weighted gene coexpression network analysis to identify key modules and genes associated with OSCC and intersected the differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA)-OSCC and GSE30784 datasets. Next, we performed survival analysis and immunohistochemistry to screen and validate the hub gene insulin-like growth factor 2 (IGF2) mRNA binding protein 2 IGF2BP2. We also used TCGA pan-cancer data to verify that IGF2BP2 was expressed at high levels in a variety of cancers and was related to a poor prognosis in patients. Furthermore, we divided patients with OSCC into high and low expression groups based on the median expression level of IGF2BP2. Gene set enrichment analysis (GSEA) showed that IGF2BP2 led to a poor prognosis in OSCC by affecting cancer-related (epithelial-mesenchymal transition, glycolysis, cell cycle, etc.) and immune-related biological functions and pathways. Single-sample GSEA (ssGSEA), CIBERSORT, and xCell algorithms helped reveal that high IGF2BP2 expression was accompanied by a significant reduction in the immune score, stromal score, and microenvironment score and a decrease in the number of infiltrating CD8+ T cells in OSCC. In addition, silencing IGF2BP2 suppressed the proliferation, migration, and invasion of OSCC cells. In general, IGF2BP2 is a potential biomarker for the progression, immunotherapy response, and prognosis of OSCC.
口腔鳞状细胞癌（OSCC）细胞在早期具有很强的侵袭和转移能力，这是其预后不良的主要原因。OSCC的早期诊断和治疗可能会降低转移率并提高生存率。本研究的目的是探索与OSCC预后和进展相关的候选生物标志物。我们进行了加权基因共表达网络分析，以识别与OSCC相关的关键模块和基因，并对癌症基因组图谱（TCGA）-OSCC和GSE30784数据集中的差异表达基因（DEG）进行了交集分析。接下来，我们进行了生存分析和免疫组织化学，以筛选和验证枢纽基因胰岛素样生长因子2（IGF2）mRNA结合蛋白2（IGF2BP2）。我们还使用TCGA泛癌数据来验证IGF2BP2在多种癌症中高表达，并且与患者的不良预后相关。此外，我们根据IGF2BP2的中位表达水平将OSCC患者分为高表达组和低表达组。基因集富集分析（GSEA）表明，IGF2BP2通过影响癌症相关（上皮-间质转化、糖酵解、细胞周期等）和免疫相关的生物学功能及通路，导致OSCC预后不良。单样本GSEA（ssGSEA）、CIBERSORT和xCell算法有助于揭示，在OSCC中，IGF2BP2高表达伴随着免疫评分、基质评分和微环境评分的显著降低以及浸润性CD8 + T细胞数量的减少。此外，沉默IGF2BP2可抑制OSCC细胞的增殖、迁移和侵袭。总体而言，IGF2BP2是OSCC进展、免疫治疗反应和预后的潜在生物标志物。
