一种新型免疫相关预后模型的开发与验证以及滑膜肉瘤的潜在转移机制
Development and validation of a novel immune-related prognostic model and the potential metastatic mechanism in synovial sarcoma.
作者信息
Huang Yufeng, Gong Ming, Lin Jiaming, Tang Qinglian, Chen Hongmin, Hu Jinxin, Deng Chuangzhong, Huang Anfei, Feng Huixiong, Song Guohui, Xu Huaiyuan, Lu Jinchang, Zhu Xiaojun, Wang Jin
机构信息
Department of Cervical Spondylosis and Spine Orthopedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, China.
出版信息
Front Immunol. 2024 Dec 10;15:1448464. doi: 10.3389/fimmu.2024.1448464. eCollection 2024.
BACKGROUND
Several clinical trials have shown that immunotherapy plays a pivotal role in the treatment of patients with metastatic synovial sarcoma. Immune-related genes (IRGs) have been demonstrated to predict the immunotherapy response in certain malignant tumours. However, the clinical significance of IRGs in patients with synovial sarcoma (SS) is still unclear.
METHODS
We first combined the immune-related ImmPort gene set to search for SS related to metastatic and differentially expressed immune-related genes (DEIRGs) in the GSE40021 dataset from the GEO database. The soft tissue sarcoma database in TCGA was used for univariate Cox regression analyses to identify DEIRGs that were related to overall survival and to build an immune-related prognostic assessment model.
RESULTS
The study screened a total of six DEIRGs that were closely related to prognosis in metastatic SS. Further analysis showed that there was no significant difference in the expression of several immune checkpoints between the two groups in the GSE40021 data. Moreover, the GREM2 and CTSS genes were significantly expressed in metastatic patients. Further verification of clinical SS tissues from our centre by RT-qPCR analysis demonstrated reduced infiltration of activated NK cells and macrophages but increased M2-type macrophages in metastatic patients. Together, our study successfully constructed an immune-related prognostic assessment model and probably explains the poor efficacy of PD-1 inhibitors for SS patients.
CONCLUSION
The research deepens our understanding of the tumor immune microenvironment and proposes a new immune mechanism for metastatic SS. Early intervention and reversal of immunosuppressive microenvironmental changes are expected to delay metastasis and improve survival.
背景
多项临床试验表明,免疫疗法在转移性滑膜肉瘤患者的治疗中起着关键作用。免疫相关基因(IRGs)已被证明可预测某些恶性肿瘤的免疫治疗反应。然而,IRGs在滑膜肉瘤(SS)患者中的临床意义仍不清楚。
方法
我们首先结合免疫相关的ImmPort基因集,在来自GEO数据库的GSE40021数据集中搜索与转移性和差异表达的免疫相关基因(DEIRGs)相关的SS。使用TCGA中的软组织肉瘤数据库进行单变量Cox回归分析,以识别与总生存期相关的DEIRGs,并建立免疫相关的预后评估模型。
结果
该研究共筛选出6个与转移性SS预后密切相关的DEIRGs。进一步分析表明,GSE40021数据中两组之间的几个免疫检查点的表达没有显著差异。此外,GREM2和CTSS基因在转移性患者中显著表达。通过RT-qPCR分析对我们中心的临床SS组织进行进一步验证,结果表明转移性患者中活化NK细胞和巨噬细胞的浸润减少,但M2型巨噬细胞增加。总之,我们的研究成功构建了一个免疫相关的预后评估模型,并可能解释了PD-1抑制剂对SS患者疗效不佳的原因。
结论
该研究加深了我们对肿瘤免疫微环境的理解,并提出了一种转移性SS的新免疫机制。早期干预和逆转免疫抑制微环境变化有望延缓转移并提高生存率。
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