研究动态
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使用空间转录组学发现结直肠癌的预后 lncRNA。

Discovery of prognostic lncRNAs in colorectal cancer using spatial transcriptomics.

发表日期:2024 Oct 10
作者: Holly R Pinkney, Cody R Ross, Timothy O Hodgson, Sharon T Pattison, Sarah D Diermeier
来源: npj Precision Oncology

摘要:

结直肠癌(CRC)表现出显着的遗传和表观遗传多样性,演变成具有不同转移潜力和治疗反应的亚克隆群体。预测 CRC 患者的转移性疾病仍然具有挑战性,这凸显了对可靠生物标志物的需求。虽然大多数治疗靶点和生物标志物的研究都集中在蛋白质上,但非编码 RNA(例如长非编码 RNA (lncRNA))构成了大部分转录组,并表现出优异的组织和癌症特异性表达。我们利用空间转录组学研究 CRC 肿瘤中的 lncRNA,与批量 RNA 测序相比,提供了更精确的细胞类型特异性表达数据。我们的分析确定了 301 个与恶性 CRC 区域相关的 lncRNA,并使用公共数据进行了验证。使用 RNA-FISH 的进一步验证揭示了三种 lncRNA(LINC01978、PLAC4 和 LINC01303),它们在 II 期肿瘤中可检测到,但在正常上皮中检测不到,并且在转移组织中上调。这些 lncRNA 具有作为转移性疾病早期风险评估生物标志物的潜力。© 2024。作者。
Colorectal cancer (CRC) exhibits significant genetic and epigenetic diversity, evolving into sub-clonal populations with varied metastatic potentials and treatment responses. Predicting metastatic disease in CRC patients remains challenging, underscoring the need for reliable biomarkers. While most research on therapeutic targets and biomarkers has focused on proteins, non-coding RNAs such as long non-coding RNAs (lncRNAs) comprise most of the transcriptome and demonstrate superior tissue- and cancer-specific expression. We utilised spatial transcriptomics to investigate lncRNAs in CRC tumours, offering more precise cell-type-specific expression data compared to bulk RNA sequencing. Our analysis identified 301 lncRNAs linked to malignant CRC regions, which we validated with public data. Further validation using RNA-FISH revealed three lncRNAs (LINC01978, PLAC4, and LINC01303) that are detectable in stage II tumours but not in normal epithelium and are upregulated in metastatic tissues. These lncRNAs hold potential as biomarkers for early risk assessment of metastatic disease.© 2024. The Author(s).