Gaëlle Angenard1, Aude Merdrignac1, Corentin Louis1, Julien Edeline1, Cédric Coulouarn2. 1. Inserm, Univ Rennes, Inra, Institut NuMeCan (Nutrition Metabolisms and Cancer), CHU Rennes, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France. 2. Inserm, Univ Rennes, Inra, Institut NuMeCan (Nutrition Metabolisms and Cancer), CHU Rennes, Centre de Lutte contre le Cancer Eugène Marquis, Rennes, France. Electronic address: cedric.coulouarn@inserm.fr.
Abstract
BACKGROUND: 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. AIM: To identify lncRNA significantly associated with the survival of patients with iCCA after tumor resection for curative intent. METHODS: 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. RESULTS: 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. CONCLUSIONS: We report a prognosis lncRNA signature in iCCA and the clinical relevance of CDKN2B-AS1 (ANRIL) overexpression in several cancers.
BACKGROUND: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. AIM: To identify lncRNA significantly associated with the survival of patients with iCCA after tumor resection for curative intent. METHODS: 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. RESULTS: 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. CONCLUSIONS: We report a prognosis lncRNA signature in iCCA and the clinical relevance of CDKN2B-AS1 (ANRIL) overexpression in several cancers.
Authors: John K Cusick; Yasmeen Alhomsy; Stephanie Wong; George Talbott; Vladimir N Uversky; Cara Hart; Nazila Hejazi; Aaron T Jacobs; Yihui Shi Journal: Biochem Biophys Rep Date: 2020-12-15
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