Inserm, Univ Rennes, Inra, Institut NuMeCan (Nutrition Metabolisms and Cancer), CHU Rennes, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France.
Inserm, Univ Rennes, Inra, Institut NuMeCan (Nutrition Metabolisms and Cancer), CHU Rennes, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France.
Dig Liver Dis. 2019 Sep;51(9):1337-1343. doi: 10.1016/j.dld.2019.03.019. Epub 2019 Apr 27.
Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide associated with an increased incidence, limited therapeutic options and absence of reliable prognostic biomarkers. Long non-coding RNAs (lncRNA) emerge as relevant biomarkers in cancer being associated with tumor progression. However, lncRNA have been poorly investigated in iCCA.
To identify lncRNA significantly associated with the survival of patients with iCCA after tumor resection for curative intent.
Gene expression profiling and Q-RT-PCR were performed from a cohort of 39 clinically well-annotated iCCA. Univariate Cox proportional hazards model with Wald Statistic was used to identify lncRNA significantly associated with overall (OS) and/or disease-free (DFS) survival.
A signature made of 9 lncRNA was identified to be significantly (P < 0.05) associated with OS and DFS, including 4 lncRNA (lnc-CDK9-1, XLOC_l2_009441, CDKN2B-AS1, HOXC13-AS) highly expressed in poor prognosis iCCA and 5 lncRNA (lnc-CCHCR1-1, lnc-AF131215.3.1, lnc-CBLB-5, COL18A1-AS2, lnc-RELL2-1) highly expressed in better prognosis iCCA. We further validated CDKN2B-AS1 (ANRIL) as a poor prognosis biomarker, not only in iCCA, but also in hepatocellular carcinoma, kidney renal clear cell carcinoma and uterine corpus endometrial carcinoma.
We report a prognosis lncRNA signature in iCCA and the clinical relevance of CDKN2B-AS1 (ANRIL) overexpression in several cancers.
肝内胆管癌（iCCA）是一种全球范围内致命的癌症，其发病率增加，治疗选择有限，且缺乏可靠的预后生物标志物。长链非编码 RNA（lncRNA）作为癌症相关的重要生物标志物，与肿瘤进展相关。然而，lncRNA 在 iCCA 中的研究甚少。
鉴定与 iCCA 患者肿瘤切除后生存显著相关的 lncRNA。
对 39 例临床特征明确的 iCCA 患者进行基因表达谱分析和 Q-RT-PCR。采用单因素 Cox 比例风险模型和 Wald 统计量鉴定与总生存期（OS）和/或无病生存期（DFS）显著相关的 lncRNA。
确定了一个由 9 个 lncRNA 组成的签名，与 OS 和 DFS 显著相关（P<0.05），其中包括 4 个在预后不良的 iCCA 中高表达的 lncRNA（lnc-CDK9-1、XLOC_l2_009441、CDKN2B-AS1、HOXC13-AS）和 5 个在预后良好的 iCCA 中高表达的 lncRNA（lnc-CCHCR1-1、lnc-AF131215.3.1、lnc-CBLB-5、COL18A1-AS2、lnc-RELL2-1）。我们进一步验证了 CDKN2B-AS1（ANRIL）不仅在 iCCA 中，而且在肝细胞癌、肾透明细胞癌和子宫内膜癌中都是预后不良的生物标志物。
我们报告了 iCCA 中一种预后 lncRNA 特征，以及 CDKN2B-AS1（ANRIL）在多种癌症中过度表达的临床相关性。
