Tian Kang, Yao Ziang, Pan Da
Department of Oncology, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China.
Department of Traditional Chinese Medicine, Peking University People's Hospital, Beijing, China.
Front Immunol. 2024 Dec 17;15:1490623. doi: 10.3389/fimmu.2024.1490623. eCollection 2024.
Esophageal squamous cell carcinoma (ESCC) remains a significant challenge in oncology due to its aggressive nature and heterogeneity. As one of the deadliest malignancies, ESCC research lags behind other cancer types. The balance between ubiquitination and deubiquitination processes plays a crucial role in cellular functions, with its disruption linked to various diseases, including cancer.
Our study utilized diverse analytical approaches, encompassing Cox regression models, single-cell RNA sequencing, intercellular communication analysis, and Gene Ontology enrichment. We also conducted mutation profiling and explored potential immunotherapeutic agents. Furthermore, cellular experiments and mouse models were performed to validate findings. These methodologies aimed to establish deubiquitination-related gene signatures (DRGS) for predicting ESCC patient outcomes and response to immunotherapy.
By integrating datasets from TCGA-ESCC and GSE53624, we developed a DRGS model based on 14 deubiquitination-related genes (DUBGs). This signature effectively forecasts ESCC prognosis, drug responsiveness, and immune cell infiltration patterns. It also influences the mutational landscape of patients. Those classified as high-risk exhibited reduced survival rates, increased genetic alterations, and more complex cellular interactions, potentially explaining their poor outcomes. Notably, and experiments identified MTOR, a key component of the signature, as a promising therapeutic target for ESCC treatment.
Our research highlights the significance of 14 DUBGs in ESCC progression. The risk score derived from this gene set enables clinical stratification of patients into distinct prognostic groups. Moreover, MTOR emerges as a potential target for personalized ESCC therapy, offering new avenues for treatment strategies.
食管鳞状细胞癌（ESCC）因其侵袭性和异质性，仍然是肿瘤学领域的一项重大挑战。作为最致命的恶性肿瘤之一，ESCC的研究落后于其他癌症类型。泛素化和去泛素化过程之间的平衡在细胞功能中起着关键作用，其破坏与包括癌症在内的各种疾病相关。
我们的研究采用了多种分析方法，包括Cox回归模型、单细胞RNA测序、细胞间通讯分析和基因本体富集分析。我们还进行了突变分析并探索了潜在的免疫治疗药物。此外，进行了细胞实验和小鼠模型以验证研究结果。这些方法旨在建立与去泛素化相关的基因特征（DRGS），以预测ESCC患者的预后和对免疫治疗的反应。
通过整合来自TCGA-ESCC和GSE53624的数据集，我们基于14个与去泛素化相关的基因（DUBG）开发了一个DRGS模型。该特征有效地预测了ESCC的预后、药物反应性和免疫细胞浸润模式。它还影响患者的突变格局。那些被归类为高风险的患者生存率降低，基因改变增加，细胞间相互作用更复杂，这可能解释了他们预后不良的原因。值得注意的是，细胞实验和小鼠实验确定该特征的关键成分MTOR是ESCC治疗的一个有前景的治疗靶点。
我们的研究强调了14个DUBG在ESCC进展中的重要性。从该基因集得出的风险评分能够将患者临床分层为不同的预后组。此外，MTOR成为个性化ESCC治疗的潜在靶点，为治疗策略提供了新途径。
