Lin Yubiao, Huang Kaida, Cai Zhezhen, Chen Yide, Feng Lihua, Gao Yingqin, Zheng Wenhui, Fan Xin, Qiu Guoqin, Zhuang Jianmin, Feng Shuitu
Department of Oncology, Xiamen Haicang Hospital, Xiamen, China.
Department of General Surgery, Xiamen Haicang Hospital, Xiamen, China.
Front Pharmacol. 2022 Jun 3;13:884090. doi: 10.3389/fphar.2022.884090. eCollection 2022.
Gastric cancer (GC) is a highly heterogeneous malignant carcinoma. This study aimed to conduct an exosome-based classification for assisting personalized therapy for GC. Based on the expression profiling of prognostic exosome-related genes, GC patients in The Cancer Genome Atlas (TCGA) cohort were classified using the unsupervised consensus clustering approach, and the reproducibility of this classification was confirmed in the GSE84437 cohort. An exosome-based gene signature was developed Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Immunological features, responses to immune checkpoint inhibitors, and genetic alterations were evaluated computational methods. Two exosome-relevant phenotypes (A and B) were clustered, and this classification was independent of immune subtypes and TCGA subtypes. Exosome-relevant phenotype B had a poorer prognosis and an inflamed tumor microenvironment (TME) relative to phenotype A. Patients with phenotype B presented higher responses to the anti-CTLA4 inhibitor. Moreover, phenotype B occurred at a higher frequency of genetic mutation than phenotype A. The exosome-based gene signature (GPX3, RGS2, MATN3, SLC7A2, and SNCG) could independently and accurately predict GC prognosis, which was linked to stromal activation and immunosuppression. Our findings offer a conceptual frame to further comprehend the roles of exosomes in immune escape mechanisms and genomic alterations of GC. More work is required to evaluate the reference value of exosome-relevant phenotypes for designing immunotherapeutic regimens.
胃癌（GC）是一种高度异质性的恶性肿瘤。本研究旨在进行基于外泌体的分类，以辅助胃癌的个性化治疗。基于预后外泌体相关基因的表达谱，使用无监督一致性聚类方法对癌症基因组图谱（TCGA）队列中的胃癌患者进行分类，并在GSE84437队列中证实了该分类的可重复性。通过最小绝对收缩和选择算子（LASSO）回归分析建立了基于外泌体的基因特征。采用计算方法评估免疫特征、对免疫检查点抑制剂的反应和基因改变。聚类出两种与外泌体相关的表型（A和B），且该分类独立于免疫亚型和TCGA亚型。与表型A相比，外泌体相关表型B的预后较差，肿瘤微环境（TME）呈炎症状态。表型B的患者对抗CTLA4抑制剂的反应更高。此外，表型B的基因突变频率高于表型A。基于外泌体的基因特征（GPX3、RGS2、MATN3、SLC7A2和SNCG）能够独立且准确地预测胃癌预后，这与基质激活和免疫抑制有关。我们的研究结果为进一步理解外泌体在胃癌免疫逃逸机制和基因组改变中的作用提供了一个概念框架。还需要更多工作来评估外泌体相关表型在设计免疫治疗方案中的参考价值。
