Shuai Yu, Zhang Xiaofang, Lavrijssen Birgit D A, Ikram M Arfan, Ruiter Rikje, Stricker Bruno, Ghanbari Mohsen
Department of Epidemiology, Erasmus MC, University Medical Center, P.O. Box 2040, Rotterdam, 3000 CA, The Netherlands.
Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
Biomark Res. 2024 Aug 13;12(1):83. doi: 10.1186/s40364-024-00626-5.
MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation of gene expression. Mounting evidence underscores the dysregulation of miRNAs to be associated with cancer development and progression by acting as tumour suppressors and oncogenes. However, their potential as biomarkers for early diagnosis of different cancers remains incompletely unraveled. We explored the relationship between plasma circulatory miRNAs and cancer risk within the population-based Rotterdam Study cohort. Plasma samples were collected at baseline (between 2002 and 2005) and miRNA levels were measured in 1,999 participants, including 169 prevalent cancer cases. The occurrence of cancer was assessed by continuous monitoring of medical records in 1,830 cancer-free participants until January 1, 2015. We assessed the association between incidence of five common cancers (blood, lung, breast, prostate, and colorectal) and 591 miRNAs well-expressed in plasma, using adjusted Cox proportional-hazards regression models. Our longitudinal analysis identified 13 miRNAs significantly associated with incident hematologic tumors surpassing the Bonferroni-corrected P < 8.46 × 10, 12 of them (miR-6124, miR-6778-5p, miR-5196, miR-654-5p, miR-4478, miR-4430, miR-4534, miR-1915-3p, miR-4644, miR-4292, miR-7111-5p, and miR-6870-5p) were also associated with prevalent hematologic tumors in the cross-sectional analysis at the baseline. In-silico analyses of the putative target genes of 13 identified miRNAs highlighted relevant genes and pathways linked to hematologic tumors. While no significant miRNA association was found for other four studied cancers, two miRNAs (miR-3157-5p and miR-3912-5p) showed nominal association with incident of three different cancer types. Overall, this study indicates that plasma levels of several miRNAs are dysregulated in hematologic tumors, highlighting their potential as biomarkers for early diagnosis as well as being involved in the pathogenesis of blood cancers.
微小RNA（miRNA）是参与基因表达转录后调控的小非编码RNA。越来越多的证据强调，miRNA的失调通过充当肿瘤抑制因子和癌基因，与癌症的发生和发展相关。然而，它们作为不同癌症早期诊断生物标志物的潜力仍未完全阐明。我们在基于人群的鹿特丹研究队列中探索了血浆循环miRNA与癌症风险之间的关系。在基线时（2002年至2005年之间）采集血浆样本，并在1999名参与者中测量miRNA水平，其中包括169例现患癌症病例。通过持续监测1830名无癌参与者的病历直至2015年1月1日来评估癌症的发生情况。我们使用校正后的Cox比例风险回归模型评估了五种常见癌症（血液、肺癌、乳腺癌、前列腺癌和结直肠癌）的发病率与591种在血浆中高表达的miRNA之间的关联。我们的纵向分析确定了13种与血液系统肿瘤发病显著相关的miRNA，超过了Bonferroni校正后的P<8.46×10，其中12种（miR-6124、miR-6778-5p、miR-5196、miR-654-5p、miR-4478、miR-4430、miR-4534、miR-1915-3p、miR-4644、miR-4292、miR-7111-5p和miR-6870-5p）在基线时的横断面分析中也与现患血液系统肿瘤相关。对13种已鉴定miRNA的假定靶基因进行的计算机分析突出了与血液系统肿瘤相关的相关基因和途径。虽然在其他四种研究的癌症中未发现显著的miRNA关联，但两种miRNA（miR-3157-5p和miR-3912-5p）与三种不同癌症类型的发病显示出名义上的关联。总体而言，这项研究表明血液系统肿瘤中几种miRNA的血浆水平失调，突出了它们作为早期诊断生物标志物的潜力以及参与血液癌症的发病机制。
