Department of Joint Surgery HongHui Hospital Xi'an Jiaotong University, Xi'an 710054, Shaanxi, China.
Department of General Practice Honghui Hospital Xi'an Jiao Tong University, Xi'an 710054, Shaanxi, China.
Mediators Inflamm. 2024 Aug 24;2024:2825971. doi: 10.1155/2024/2825971. eCollection 2024.
Extracellular vesicles play an important role in the progression of pancreatic adenocarcinoma (PAAD) through the transfer of proteins, mRNAs, and long noncoding RNAs (lncRNAs). However, the intricate interplay between extracellular vesicles-related lncRNAs and the tumor microenvironment (TME) remains poorly elucidated. Consequently, our investigation aimed to delineate the association between extracellular vesicles-related lncRNAs and the PAAD microenvironment. Initially, we identified differentially expressed lncRNAs (DELs) from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) project datasets. Subsequently, we validated the expression of these DELs within extracellular vesicles and assessed their prognostic implications in PAAD using the GSE133684 and TCGA datasets. Multiomics data were analyzed comprehensively, including genomic landscape, functional annotation, immune profiles, and therapeutic responses. Differential expression of selected lncRNAs in both cellular and exosomal fractions of PAAD was further confirmed through quantitative polymerase chain reaction (qPCR). Eight DELs were identified from TCGA and GTEx datasets, and two exosomal lncRNAs exhibited a significant correlation with overall survival, warranting further investigation. Specifically, elevated expression of LINC00996 correlated positively with immune infiltration and enhanced response to immunotherapy. Conversely, heightened expression of TRHED-AS1 was associated with compromised immune cell infiltration and diminished responsiveness to immunotherapy. Our study establishes a compelling link between two extracellular vesicles-related gene signatures, prognosis, and immune infiltration in PAAD. Notably, these signatures serve as robust prognostic indicators for PAAD patients, offering valuable insights for the strategic selection of immunotherapeutic interventions.
细胞外囊泡通过转移蛋白质、mRNA 和长链非编码 RNA（lncRNA）在胰腺导管腺癌（PAAD）的进展中发挥重要作用。然而，细胞外囊泡相关 lncRNA 与肿瘤微环境（TME）之间的复杂相互作用仍未得到充分阐明。因此，我们的研究旨在描绘细胞外囊泡相关 lncRNA 与 PAAD 微环境之间的关联。首先，我们从癌症基因组图谱（TCGA）和基因型组织表达（GTEx）项目数据集确定差异表达的 lncRNA（DEL）。随后，我们在细胞外囊泡中验证这些 DEL 的表达，并使用 GSE133684 和 TCGA 数据集评估其在 PAAD 中的预后意义。综合分析多组学数据，包括基因组景观、功能注释、免疫特征和治疗反应。通过定量聚合酶链反应（qPCR）进一步确认了所选 lncRNA 在 PAAD 的细胞和外泌体部分中的差异表达。从 TCGA 和 GTEx 数据集确定了 8 个 DEL，两个外泌体 lncRNA 的表达与总生存期显著相关，值得进一步研究。具体而言，LINC00996 的表达升高与免疫浸润呈正相关，并增强了对免疫治疗的反应。相反，TRHED-AS1 的表达升高与免疫细胞浸润受损和对免疫治疗反应降低相关。我们的研究在 PAAD 中建立了两个细胞外囊泡相关基因特征、预后和免疫浸润之间的强有力联系。值得注意的是，这些特征可作为 PAAD 患者的强大预后指标，为免疫治疗干预的策略选择提供有价值的见解。
