RRC ID 52144
Author Komatsu H, Masuda T, Iguchi T, Nambara S, Sato K, Hu Q, Hirata H, Ito S, Eguchi H, Sugimachi K, Eguchi H, Doki Y, Mori M, Mimori K.
Title Clinical Significance of FANCD2 Gene Expression and its Association with Tumor Progression in Hepatocellular Carcinoma.
Journal Anticancer Res.
Abstract BACKGROUND/AIM:Fanconi anemia complementation group D2 (FANCD2) gene is vitally involved in DNA damage responses. We investigated the clinical significance of FANCD2 expression in hepatocellular carcinoma (HCC).
PATIENTS AND METHODS:FANCD2 mRNA expression of resected HCC tissues was assessed in two HCC cohorts; Our cases (n=111), and The Cancer Genome Atlas (TCGA; n=371). Gene set enrichment analysis (GSEA) was conducted using the TCGA dataset. Proliferation and invasion assays were performed using siRNAs, and the effect of inhibition of the mechanistic target of rapamycin (mTOR) pathway was evaluated.
RESULTS:FANCD2 expression was up-regulated in tumor tissues. Cases with high FANCD2 expression had poorer prognoses in both cohorts, and were associated with larger tumor size and invasive phenotypes. FANCD2 knockdown attenuated proliferation and invasion of HCC cells. FANCD2 expression was suppressed by mTOR inhibition. GSEA supported these findings.
CONCLUSION:Elevated FANCD2 expression in HCC could be a novel biomarker for poor prognosis with potential therapeutic relevance.
Volume 37(3)
Pages 1083-1090
Published 2017-3
DOI 10.21873/anticanres.11420
PII 37/3/1083
PMID 28314268
MeSH Aged Biomarkers, Tumor / metabolism Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism* Cell Proliferation Cohort Studies DNA Damage Disease Progression Fanconi Anemia Complementation Group D2 Protein / genetics Fanconi Anemia Complementation Group D2 Protein / metabolism* Female Gene Expression Profiling* Hep G2 Cells Humans Liver Neoplasms / genetics Liver Neoplasms / metabolism* Male Middle Aged Neoplasm Invasiveness Phenotype Prognosis RNA, Small Interfering / metabolism Reverse Transcriptase Polymerase Chain Reaction TOR Serine-Threonine Kinases / metabolism
IF 1.865
Resource
Human and Animal Cells PLC/PRF/5(ECA85061113)