Zhou Meng, Hu Long, Zhang Zicheng, Wu Nan, Sun Jie, Su Jianzhong
School of Ophthalmology & Optometry and Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Mol Ther Nucleic Acids. 2018 Sep 7;12:518-529. doi: 10.1016/j.omtn.2018.06.007. Epub 2018 Jun 26.
Patients with colon cancer are often faced a high risk of disease recurrence within 5 years of treatment that is the major cause of cancer mortality. Reliable molecular markers were required to improve the most effective personalized therapy. Here, we identified a recurrence-associated six-lncRNA (long non-coding RNA) signature (LINC0184, AC105243.1, LOC101928168, ILF3-AS1, MIR31HG, and AC006329.1) that can effectively distinguish between high and low risk of cancer recurrence from 389 patients of a discovery dataset, and validated its robust performance in four independent datasets comprising a total of 906 colon cancer patients. We found that the six-lncRNA signature was an independent predictive factor of disease recurrence in multivariate analysis and was superior to the performance of clinical factors and known gene signature. Furthermore, in silico functional analysis showed that the six-lncRNA-signature-associated coding genes are significantly enriched in proliferation and angiogenesis, cell death, as well as critical cancer pathways that could play important roles in colon cancer recurrence. Together, the six-lncRNA signature holds great potential for recurrence risk assessment and personalized management of colon cancer patients.
结肠癌患者在治疗后的5年内常常面临疾病复发的高风险,这是癌症死亡的主要原因。需要可靠的分子标志物来改善最有效的个性化治疗。在此,我们鉴定出一种与复发相关的六lncRNA(长链非编码RNA)特征(LINC0184、AC105243.1、LOC101928168、ILF3-AS1、MIR31HG和AC006329.1),其能够从一个发现数据集中的389例患者有效区分癌症复发的高风险和低风险,并在总共包含906例结肠癌患者的四个独立数据集中验证了其稳健性能。我们发现在多变量分析中,六lncRNA特征是疾病复发的独立预测因素,并且优于临床因素和已知基因特征的性能。此外,计算机功能分析表明,与六lncRNA特征相关的编码基因在增殖和血管生成、细胞死亡以及可能在结肠癌复发中起重要作用的关键癌症通路中显著富集。总之,六lncRNA特征在结肠癌患者的复发风险评估和个性化管理方面具有巨大潜力。