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

Biomarkers, Tumor / genetics Carcinoma, Renal Cell / pathology DEAD-box RNA Helicases / genetics Gene Expression Regulation, Neoplastic Humans Kidney Neoplasms / pathology Necrosis / genetics Prognosis RNA, Messenger / metabolism Von Hippel-Lindau Tumor Suppressor Protein / genetics
DDX41 Prognostic predictor Renal cell carcinoma Tumor necrosis VHL loss

Journal

Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460

Informations de publication

Date de publication:
10 2022
Historique:
received: 05 02 2022
revised: 21 06 2022
accepted: 04 07 2022
pubmed: 3 8 2022
medline: 28 9 2022
entrez: 2 8 2022
Statut: ppublish

Résumé

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. 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. 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. DDX41 expression is associated with TN in ccRCC and leads to a worse prognosis in cooperation with VHL loss.

Sections du résumé

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.

Identifiants

DOI: 10.1016/j.urolonc.2022.07.001 PMID: 35918249
pubmed: 35918249
pii: S1078-1439(22)00258-7
doi: 10.1016/j.urolonc.2022.07.001
pii:
doi:

Substances chimiques

Biomarkers, Tumor 0
RNA, Messenger 0
Von Hippel-Lindau Tumor Suppressor Protein EC 2.3.2.27
DDX41 protein, human EC 3.6.1.-
DEAD-box RNA Helicases EC 3.6.4.13
VHL protein, human EC 6.3.2.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

456.e9-456.e18

Informations de copyright

Copyright © 2022. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Conflict of interest All authors declare no conflicts of interest.

Auteurs

Kohei Kobatake (K)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan. Electronic address: kkobatake@hiroshima-u.ac.jp.

Kenichiro Ikeda (K)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Yuichiro Nakata (Y)

Chromatin Dynamics in Stem Cells and Cancer Lab, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL.

Norimasa Yamasaki (N)

Department of Disease Model, Research Institute of Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima, Japan.

Akinori Kanai (A)

Laboratory of Systems Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa-shi, Chiba, Japan.

Yohei Sekino (Y)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Kenshiro Takemoto (K)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Takafumi Fukushima (T)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Takashi Babasaki (T)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Hiroyuki Kitano (H)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Keisuke Goto (K)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Tetsutaro Hayashi (T)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Kazuhiro Sentani (K)

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Jun Teishima (J)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

Osamu Kaminuima (O)

Department of Disease Model, Research Institute of Radiation Biology and Medicine, Hiroshima University, Minami-ku, Hiroshima, Japan.

Nobuyuki Hinata (N)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.

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Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › DDX41 expression is associated with tumor...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › Néphrocarcinome › DDX41 expression is associated with tumor...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › RNA nucleotidyltransferases › RNA helicases › DEAD-box RNA helicases › DDX41 expression is associated with tumor...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › DDX41 expression is associated with tumor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › DDX41 expression is associated with tumor...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › DDX41 expression is associated with tumor...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Nécrose › DDX41 expression is associated with tumor...
questionsmedicales.fr › Diagnostic › Pronostic › DDX41 expression is associated with tumor...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › DDX41 expression is associated with tumor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Protéine Von Hippel-Lindau supresseur de tumeur › DDX41 expression is associated with tumor...