論文

国際誌
2022年7月30日

DDX41 expression is associated with tumor necrosis in clear cell renal cell carcinoma and in cooperation with VHL loss leads to worse prognosis.

Urologic oncology
  • Kohei Kobatake
  • ,
  • Kenichiro Ikeda
  • ,
  • Yuichiro Nakata
  • ,
  • Norimasa Yamasaki
  • ,
  • Akinori Kanai
  • ,
  • Yohei Sekino
  • ,
  • Kenshiro Takemoto
  • ,
  • Takafumi Fukushima
  • ,
  • Takashi Babasaki
  • ,
  • Hiroyuki Kitano
  • ,
  • Keisuke Goto
  • ,
  • Tetsutaro Hayashi
  • ,
  • Kazuhiro Sentani
  • ,
  • Jun Teishima
  • ,
  • Osamu Kaminuima
  • ,
  • Nobuyuki Hinata

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.urolonc.2022.07.001

BACKGROUND: Histologic tumor necrosis (TN) is a well-established independent prognostic indicator in patients treated surgically for clear cell renal cell carcinoma (ccRCC). However, the precise mechanisms by which TN alters disease progression remain unknown. The DEAD-box protein DDX41, a member of a large family of helicases, has been characterized as a pattern recognition receptor against an array of double-stranded (ds)DNA produced from bacteria, dsDNA viruses, and nearby cells that have released dsDNA fragments through necrosis. We hypothesized that DDX41 expression may be upregulated in ccRCC with TN, leading to worse prognosis. METHODS: Relationship between the presence of TN and DDX41 expression were examined using The Cancer Genome Atlas data sets or using ccRCC samples in our institution. Further, the molecular functions of DDX41 were investigated with human ccRCC cells. RESULTS: The presence of TN was significantly associated with the upregulation of mRNA and protein expression of DDX41 in the 2different patient cohorts with ccRCC. In addition, the mRNA and protein expression levels of DDX41 revealed a worse prognosis. In vitro analyses with ccRCC cells revealed that DDX41 expression promotes tumor-promoting activity. Furthermore, VHL loss, 1of the most common features in ccRCC, was shown to play an extremely important role in increasing the expression of the CXCL family in DDX41-expressing ccRCC, leading to the acquisition of a worse malignant phenotype. CONCLUSIONS: DDX41 expression is associated with TN in ccRCC and leads to a worse prognosis in cooperation with VHL loss.

リンク情報
DOI
https://doi.org/10.1016/j.urolonc.2022.07.001
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35918249
ID情報
  • DOI : 10.1016/j.urolonc.2022.07.001
  • PubMed ID : 35918249

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