Fang Wei, Chen Shan, Wan Di, Peng Yanhui, Yang Xiaoqin
Stomatological Hospital, Southern Medical University, Guangzhou, China.
Department of Stomatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Oncology. 2025;103(3):237-252. doi: 10.1159/000540977. Epub 2024 Sep 20.
Tongue squamous cell carcinoma (TSCC)
We obtained mRNA profiles and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (TCGA-TSCC and GSE41116, respectively). The TSCC samples from the TCGA-TSCC cohort were randomly divided into TCGA training and TCGA test datasets at a 7:3 ratio. Next, a disease-free survival (DFS) prognostic risk model was established on the basis of univariate and stepwise multivariate Cox regression analyses of the TCGA training cohort. Moreover, prognostic genes were screened. The model was subsequently evaluated and validated using the TCGA test and GSE41116 datasets. In addition, the prognostic genes were validated in the human TSCC cell line UM1 and the human oral keratinocyte (HOK) cell line using quantitative real-time polymerase chain reaction (qRT-PCR) analysis.
A total of 70 candidate genes related to invasion were identified in the TCGA-TSCC cohort. DFS data were subsequently constructed, and 6 prognostic genes, HMGN2, MYL12B, ACTB, PPP1CA, PSMB9, and IFITM3, were identified. The TSCC samples were divided into high- and low-risk groups in the TCGA training, TCGA test, and GSE41116 cohorts, respectively. In particular, patients with TSCC in the low-risk group had longer DFS than those in the high-risk group. Furthermore, qRT-PCR analysis confirmed that the expression levels of the 6 prognostic genes were significantly greater in the TSCC cell line UM1 than in the HOK cell line.
This study identified new invasion-related target genes related to poor prognosis in TSCC patients, providing new insights into the underlying mechanisms of TSCC invasion.
舌鳞状细胞癌(TSCC)是一种常见的恶性肿瘤类型,具有侵袭性强和预后差的特点。迄今为止,临床实践中尚无用于TSCC患者预后分层的侵袭相关基因表达特征。本研究旨在评估侵袭相关基因对TSCC患者预后的影响。
我们从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)(分别为TCGA-TSCC和GSE41116)中获取了mRNA谱和临床数据。将TCGA-TSCC队列中的TSCC样本以7:3的比例随机分为TCGA训练集和TCGA测试集。接下来,基于TCGA训练队列的单因素和逐步多因素Cox回归分析,建立了无病生存(DFS)预后风险模型。此外,筛选了预后基因。随后使用TCGA测试集和GSE41116数据集对该模型进行评估和验证。此外,使用定量实时聚合酶链反应(qRT-PCR)分析在人TSCC细胞系UM1和人口腔角质形成细胞(HOK)细胞系中验证了预后基因。
在TCGA-TSCC队列中总共鉴定出70个与侵袭相关的候选基因。随后构建了DFS数据,并鉴定出6个预后基因,即HMGN2、MYL12B、ACTB、PPP1CA、PSMB9和IFITM3。在TCGA训练集、TCGA测试集和GSE41116队列中,TSCC样本分别分为高风险组和低风险组。特别是,低风险组的TSCC患者的DFS比高风险组的患者更长。此外,qRT-PCR分析证实,6个预后基因在TSCC细胞系UM1中的表达水平明显高于HOK细胞系。
本研究鉴定了与TSCC患者预后不良相关的新的侵袭相关靶基因,为TSCC侵袭的潜在机制提供了新的见解。