Westermann Luisa, Diergaarde Brenda, Heidegger Simon, Poeck Hendrik, Szczepański Mirosław J, Reichert Torsten E, Spoerl Silvia, Whiteside Theresa L, Spoerl Steffen, Ludwig Nils
Oral and Maxillofacial Surgery, University Hospital Regensburg, Regensburg, Germany.
Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Clin Transl Oncol. 2025 Jan 8. doi: 10.1007/s12094-024-03796-8.
Small extracellular vesicles (sEV) released by tumor cells (tumor-derived sEV; TEX) mediate intercellular communication between tumor and non-malignant cells and were shown to impact disease progression. This study investigates the relationship between the expression levels of the vesiculation-related genes linked to sEV production and the tumor microenvironment (TME).
Two independent gene sets were analyzed, both previously linked to sEV production in various non-malignant or malignant cells. Expression profiles were compared among 28 tumor types listed in the Cancer Genome Atlas (TCGA). Gene expression and survival analysis (GEPIA2), immunogenomic analysis (TISIDB), and genomic analysis (GSCA) were performed.
Vesiculation-related genes were overexpressed in tissues of most tumor types compared to healthy tissues, and high expression levels were associated with worse overall survival in cervical squamous cell carcinoma, kidney chromophobe, lower grade glioma, hepatocellular carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma but with improved overall survival in kidney renal clear cell carcinoma. Expression of these signatures correlated with an increased abundance of infiltrating CD4( +) T cells and dendritic cells, a decreased abundance of B cells and eosinophils, and activation of tumor cell apoptosis and epithelial-mesenchymal transition pathways in all tumor types. 17-AAG was identified as a potential drug candidate to target tumors with elevated expression of vesiculation-related genes.
Vesiculation-related genes were associated with distinct immunological and genomic landscapes further emphasizing the important role of TEX in cancer progression.
肿瘤细胞释放的小细胞外囊泡（sEV；肿瘤来源的sEV，即TEX）介导肿瘤细胞与非恶性细胞之间的细胞间通讯，并已显示出影响疾病进展。本研究调查了与sEV产生相关的囊泡化相关基因的表达水平与肿瘤微环境（TME）之间的关系。
分析了两个独立的基因集，这两个基因集之前都与各种非恶性或恶性细胞中的sEV产生有关。比较了癌症基因组图谱（TCGA）中列出的28种肿瘤类型的表达谱。进行了基因表达和生存分析（GEPIA2）、免疫基因组分析（TISIDB）和基因组分析（GSCA）。
与健康组织相比，大多数肿瘤类型的组织中囊泡化相关基因过表达，高表达水平与宫颈鳞状细胞癌、肾嫌色细胞癌、低级别胶质瘤、肝细胞癌、肺鳞状细胞癌和胰腺腺癌的总体生存率较差相关，但与肾透明细胞癌的总体生存率提高相关。这些特征的表达与所有肿瘤类型中浸润性CD4(+) T细胞和树突状细胞丰度增加、B细胞和嗜酸性粒细胞丰度降低以及肿瘤细胞凋亡和上皮-间质转化途径的激活相关。17-AAG被确定为靶向囊泡化相关基因高表达肿瘤的潜在候选药物。
囊泡化相关基因与不同的免疫和基因组格局相关，进一步强调了TEX在癌症进展中的重要作用。
