Pinkney Holly R, Ross Cody R, Hodgson Timothy O, Pattison Sharon T, Diermeier Sarah D
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Awanui Laboratories, Dunedin, New Zealand.
NPJ Precis Oncol. 2024 Oct 10;8(1):230. doi: 10.1038/s41698-024-00728-1.
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.
结直肠癌（CRC）表现出显著的遗传和表观遗传多样性，会演变成具有不同转移潜能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。虽然大多数关于治疗靶点和生物标志物的研究都集中在蛋白质上，但长链非编码RNA（lncRNA）等非编码RNA构成了转录组的大部分，并表现出卓越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，它能提供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，并通过公开数据进行了验证。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，但在正常上皮中未检测到，且在转移组织中上调。这些lncRNA有望作为转移性疾病早期风险评估的生物标志物。
