Fanconi Anemia Complementation Group E, a DNA Repair-Related Gene, Is a Potential Marker of Poor Prognosis in Hepatocellular Carcinoma

Junichi Takahashi, Takaaki Masuda, Akihiro Kitagawa, Taro Tobo, Yusuke Nakano, Tadashi Abe, Yuki Ando, Keisuke Kosai, Yuta Kobayashi, Yoshihiro Matsumoto, Tomoharu Yoshizumi, Masaki Mori, Koshi Mimori

研究成果: ジャーナルへの寄稿学術誌査読

抄録

Introduction: Fanconi anemia complementation group E (FANCE) is a Fanconi anemia (FA) pathway gene that regulates DNA repair. We evaluated the clinical relevance of FANCE expression in hepatocellular carcinoma (HCC). Methods: First, the associations between the expression of FA pathway genes including FANCE and clinical outcomes in HCC patients were analyzed in 2 independent cohorts: The Cancer Genome Atlas (TCGA, n = 373) and our patient cohort (n = 53). Localization of FANCE expression in HCC tissues was observed by immunohistochemical staining. Gene set enrichment analysis (GSEA) and gene network analysis (SiGN_BN) were conducted using the TCGA dataset. Next, an in vitro proliferation assay was performed using FANCE-knockdown HCC cell lines (HuH7 and HepG2). The association between mRNA expression of FANCE and that of DNA damage response genes in HCC was analyzed using TCGA and Cancer Cell Line Encyclopedia datasets. Finally, the association between FANCE mRNA expression and overall survival (OS) in various digestive carcinomas was analyzed using TCGA data. Results: FANCE was highly expressed in HCC cells. Multivariate analysis indicated that high FANCE mRNA expression was an independent factor predicting poor OS. GSEA revealed a positive relationship between enhanced FANCE expression and E2F and MYC target gene expression in HCC tissues. FANCE knockdown attenuated the proliferation of HCC cells, as well as reduced cdc25A expression and elevated histone H3 pSer10 expression. SiGN_BN revealed that FANCE mRNA expression was positively correlated with DNA damage response genes (H2A histone family member X and checkpoint kinase 1) in HCC tissues. Significant effects of high FANCE expression on OS were observed in hepatobiliary pancreatic carcinomas, including HCC. Conclusions: FANCE may provide a potential therapeutic target and biomarker of poor prognosis in HCC, possibly by facilitating tumor proliferation, which is mediated partly by cell cycle signaling activation.

本文言語英語
ページ(範囲)101-113
ページ数13
ジャーナルOncology
100
2
DOI
出版ステータス出版済み - 1月 1 2022

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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