State Key Laboratory of Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
State Key Laboratory of Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
Mol Oncol. 2014 Dec;8(8):1393-403. doi: 10.1016/j.molonc.2014.05.010. Epub 2014 Jun 2.
Colorectal cancer (CRC) is a heterogeneous disease in terms of clinical behavior and response to therapy. Increasing evidence suggests that long noncoding RNAs (lncRNAs) are frequently aberrantly expressed in cancers, and some of them have been implicated in CRC biogenesis and prognosis. Using an lncRNA-mining approach, we constructed lncRNAs expression profiles in approximately 888 CRC samples. By applying unsupervised consensus clustering to LncRNA expression profiles, we identified five distinct molecular subtypes of CRC with different biological pathways and phenotypically distinct in their clinical outcome in both univariate and multivariate analysis. The prognostic significance of the lncRNA-based classifier was confirmed in independent patient cohorts. Further analysis revealed that most of the signature lncRNAs positively correlated with somatic copy number alterations (SCNAs). This lncRNAs-based classification schema thus provides a molecular classification applicable to individual tumors that has implications to influence treatment decisions.
结直肠癌(CRC)在临床行为和对治疗的反应方面是一种异质性疾病。越来越多的证据表明,长链非编码 RNA(lncRNA)在癌症中经常异常表达,其中一些与 CRC 的发生和预后有关。我们使用 lncRNA 挖掘方法,构建了大约 888 例 CRC 样本中的 lncRNA 表达谱。通过对 LncRNA 表达谱进行无监督共识聚类,我们确定了 CRC 的五个不同的分子亚型,它们具有不同的生物学途径,在单变量和多变量分析中表型上的临床结局也有明显的不同。基于 lncRNA 的分类器的预后意义在独立的患者队列中得到了证实。进一步的分析表明,该signature lncRNAs 大多数与体细胞拷贝数改变(SCNAs)呈正相关。因此,这种基于 lncRNAs 的分类方案为个体肿瘤提供了一种分子分类,这对影响治疗决策具有重要意义。