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胃癌中转座元件表达的空间和细胞特征。

The spatial and cellular portrait of transposable element expression during gastric cancer.

机构信息

Centro de Genómica Avanzada de Talca, Talca, Chile.

出版信息

Sci Rep. 2024 Sep 30;14(1):22727. doi: 10.1038/s41598-024-73744-7.

Abstract

Gastric Cancer (GC) is a lethal malignancy, with urgent need for the discovery of novel biomarkers for its early detection. I previously showed that Transposable Elements (TEs) become activated in early GC (EGC), suggesting a role in gene expression. Here, I follow-up on that evidence using single-cell data from gastritis to EGC, and show that TEs are expressed and follow the disease progression, with 2,430 of them being cell populations markers. Pseudotemporal trajectory modeling revealed 111 TEs associated with the origination of cancer cells. Analysis of spatial data from GC also confirms TE expression, with 204 TEs being spatially enriched in the tumor regions and the tumor microenvironment, hinting at a role of TEs in tumorigenesis. Finally, a network of TE-mediated gene regulation was modeled, indicating that ~ 2,000 genes could be modulated by TEs, with ~ 500 of them already implicated in cancer. These results suggest that TEs might play a functional role in GC progression, and highlights them as potential biomarker for its early detection.

摘要

胃癌(GC)是一种致命的恶性肿瘤,迫切需要发现新的生物标志物来进行早期检测。我之前曾表明,转座元件(TEs)在早期胃癌(EGC)中被激活,提示它们在基因表达中发挥作用。在这里,我使用从胃炎到 EGC 的单细胞数据来跟进这一证据,并表明 TEs 被表达并遵循疾病进展,其中有 2430 个是细胞群体标志物。拟时间轨迹建模揭示了 111 个与癌细胞起源相关的 TEs。对来自 GC 的空间数据的分析也证实了 TE 的表达,其中 204 个 TEs 在肿瘤区域和肿瘤微环境中空间富集,暗示 TEs 在肿瘤发生中起作用。最后,构建了一个由 TE 介导的基因调控网络,表明大约 2000 个基因可以被 TEs 调节,其中大约 500 个已经与癌症有关。这些结果表明,TEs 可能在 GC 进展中发挥功能作用,并强调它们是早期检测的潜在生物标志物。

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