Clinical Significance ofFANCD2Gene Expression and its Association with Tumor Progression in Hepatocellular Carcinoma.
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).



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.



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.



Elevated FANCD2 expression in HCC could be a novel biomarker for poor prognosis with potential therapeutic relevance.
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.|Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Hisateru
H
Komatsu
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Takaaki
T
Masuda
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Tomohiro
T
Iguchi
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Sho
S
Nambara
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Kuniaki
K
Sato
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Quingjang
Q
Hu
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Hidenari
H
Hirata
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Shuhei
S
Ito
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Hidetoshi
H
Eguchi
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Keishi
K
Sugimachi
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Hidetoshi
H
Eguchi
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Yuichiro
Y
Doki
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Masaki
M
Mori
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan kmimori@beppu.kyushu-u.ac.jp.
Koshi
K
Mimori
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D015331:Cohort Studies; D004249:DNA Damage; D018450:Disease Progression; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D014408:Biomarkers, Tumor; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D034741:RNA, Small Interfering; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
FANCD2; hepatocellular carcinoma; mTOR inhibitor; prognostic biomarker