研究动态
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ANXA5 预测头颈鳞状细胞癌的预后和免疫反应并介导增殖和迁移。

ANXA5 predicts prognosis and immune response and mediates proliferation and migration in head and neck squamous cell carcinoma.

发表日期:2024 Aug 19
作者: Donghui Yang, Huikuan Chen, Zheng Zhou, Jinfei Guo
来源: Immunity & Ageing

摘要:

头颈鳞状细胞癌 (HNSCC) 是一种常见的恶性肿瘤,其发展过程常常被忽视。通常,这些肿瘤在晚期才被识别,导致成功治疗的机会相对较低。失巢凋亡是对抗肿瘤细胞扩散的天然防御,这意味着规避失巢凋亡可以有效抑制肿瘤转移。尽管如此,针对 HNSCC 背景下的失巢凋亡的研究仍然很少。失巢凋亡相关基因 (ARG) 通过使用 GeneCards 和 Harmonizome 数据库进行了鉴定。这些基因的表达数据和相关临床特征是从癌症基因组图谱(TCGA)和基因表达综合(GEO)数据库下载的。开发了 LASSO 回归和预后风险评分模型以确定其预后意义。该分析包括使用 CIBERSORT 算法来量化免疫和基质细胞的存在。此外,在体外和体内,我们证实了独立预测预后的基因的蛋白质和 mRNA 的表达和功能作用。该研究确定了与预后相关的八个基因(ANXA5、BAK1、CDKN2A、PPARG、CCR7、MAPK11、CRYAB、CRYBA1) )并开发了一个预后模型,可以有效预测 HNSCC 患者的生存结果。较高的生存可能性与较低的风险评分相关。此外,还发现免疫和风险评分之间存在显着关系,ANXA5缺失促进了活化T细胞对HNSCC细胞的杀伤。在筛选过程中,发现65种不同化疗药物在比较高风险和低风险类别时IC50值存在显着差异。 ANXA5 成为具有独立预后意义的基因,与非肿瘤组织相比,HNSCC 组织中的蛋白质和 mRNA 水平显着升高。 ANXA5 基因活性的抑制导致 HNSCC 细胞的生长和迁移率大幅下降。动物模型实验表明,抑制ANXA5可抑制HNSCC在体内的生长和迁移。通过生物信息学,开发了高精度的预后风险模型,为HNSCC患者的生存率和免疫反应提供了有价值的见解。 ANXA5 被强调为已识别基因中的一个重要预后因素,表明它有望成为 HNSCC 患者的潜在治疗靶点。版权所有 © 2024。由 Elsevier B.V. 出版。
Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that often develops unnoticed. Typically, these tumors are identified at advanced stages, resulting in a relatively low chance of successful treatment. Anoikis serves as a natural defense against the spread of tumor cells, meaning circumventing anoikis can effectively inhibit tumor metastasis. Nonetheless, studies focusing on anoikis in the context of HNSCC remain scarce.Anoikis-related genes (ARGs) were identified by using the GeneCards and Harmonizome databases. Expression data of these genes and relevant clinical features were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A LASSO regression and a prognostic risk score model were developed to determine their prognostic significance. The analysis included the use of the CIBERSORT algorithm to quantify immune and stromal cell presence. Furthermore, in vitro and in vivo, we confirmed the expression and functional roles of proteins and mRNA of genes independently predictive of prognosis.The study identified eight genes linked to prognosis (ANXA5, BAK1, CDKN2A, PPARG, CCR7, MAPK11, CRYAB, CRYBA1) and developed a prognostic model that effectively forecasts the survival outcomes for patients with HNSCC. A higher survival likelihood is associated with lower risk scores. In addition, a significant relationship was found between immune and risk score, and ANXA5 deletion promoted the killing of HNSCC cells by activated T cells. During the screening process, 65 different chemotherapeutic drugs were found to have significant differences in IC50 values when comparing high- and low-risk categories. ANXA5 emerged as a gene with independent prognostic significance, exhibiting notably elevated protein and mRNA levels in HNSCC tissue compared to non-tumorous tissue. The suppression of ANXA5 gene activity resulted in a substantial decrease in both the growth and mobility of HNSCC cells. Animal model experiments demonstrated that inhibiting ANXA5 suppressed HNSCC growth and migration in vivo.Through bioinformatics, a prognostic risk model of high precision was developed, offering valuable insights into the survival rates and immune responses in patients with HNSCC. ANXA5 is highlighted as a significant prognostic factor among the identified genes, indicating its promise as a potential therapeutic target for those with HNSCC.Copyright © 2024. Published by Elsevier B.V.