Clinical Significance of FANCD2 Gene Expression and its Association with Tumor Progression in Hepatocellular Carcinoma

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.

Keywords: FANCD2; hepatocellular carcinoma; mTOR inhibitor; prognostic biomarker.