PMID- 37226638
OWN - NLM
STAT- MEDLINE
DCOM- 20230803
LR  - 20230804
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 114
IP  - 8
DP  - 2023 Aug
TI  - Copy number gain of ACTN4 is associated with poor prognosis in patients with 
      upper urinary tract urothelial carcinoma.
PG  - 3411-3422
LID - 10.1111/cas.15841 [doi]
AB  - alpha-Actinin4 (ACTN4), an isoform of non-muscular alpha-actinin, is involved in 
      enhancing cell motility and promoting cancer infiltration and metastasis in 
      various cancers. However, information remains limited regarding the pathological 
      significance of ACTN4 expression in upper urinary tract urothelial carcinomas 
      (UUTUCs). We obtained tumor samples from 168 consecutive patients with newly 
      diagnosed UUTUCs (92 with renal pelvic cancers and 76 with ureteral cancers), who 
      were treated with nephroureterectomy or partial ureterectomy, and analyzed the 
      expression of the ACTN4 protein and the amplification of ACTN4 using 
      immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. 
      The median follow-up duration was 65 months. Among 168 cases, 49 (29%) showed 
      ACTN4 protein overexpression and 25 (15%) showed copy number gain (>/=4 copies per 
      cell) of ACTN4. The copy number gain of ACTN4 detected using FISH significantly 
      correlated with ACTN4 protein overexpression and several adverse 
      clinicopathological factors, including higher pathological T stage, 
      lymphovascular invasion, lymph node metastasis, positive surgical margin, 
      concomitant subtype histology, and non-papillary gross finding. Cox univariate 
      regression analyses revealed that both copy number gain of ACTN4 and ACTN4 
      protein overexpression were significant risk factors for extraurothelial 
      recurrence and death (each p < 0.0001), but multivariate analysis revealed that 
      only copy number gain of ACTN4 was an independent risk factor for extraurothelial 
      recurrence and death (p = 0.038 and 0.027, hazard ratio = 2.16 and 2.17, 
      respectively). This is the first study demonstrating the aberrant expression 
      status of ACTN4 in UUTUC and indicating its putative usefulness as a prognostic 
      indicator in patients with UUTUC.
CI  - (c) 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Cancer Association.
FAU - Kawamura, Kazuki
AU  - Kawamura K
AD  - Department of Urology, National Defense Medical College, Tokorozawa, Japan.
AD  - Department of Basic Pathology, National Defense Medical College, Tokorozawa, 
      Japan.
FAU - Miyai, Kosuke
AU  - Miyai K
AUID- ORCID: 0000-0003-1776-3541
AD  - Department of Basic Pathology, National Defense Medical College, Tokorozawa, 
      Japan.
AD  - Department of Laboratory Medicine, National Defense Medical College, Tokorozawa, 
      Japan.
FAU - Sato, Kimiya
AU  - Sato K
AD  - Department of Basic Pathology, National Defense Medical College, Tokorozawa, 
      Japan.
FAU - Matsukuma, Susumu
AU  - Matsukuma S
AD  - Department of Laboratory Medicine, National Defense Medical College, Tokorozawa, 
      Japan.
FAU - Honda, Kazufumi
AU  - Honda K
AUID- ORCID: 0000-0003-1321-5345
AD  - Department of Bioregulation, Graduate School of Medicine, Nippon Medical School, 
      Bunkyo-ku, Japan.
FAU - Ito, Keiichi
AU  - Ito K
AUID- ORCID: 0000-0001-8524-2903
AD  - Department of Urology, National Defense Medical College, Tokorozawa, Japan.
FAU - Tsuda, Hitoshi
AU  - Tsuda H
AD  - Department of Basic Pathology, National Defense Medical College, Tokorozawa, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20230524
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (ACTN4 protein, human)
RN  - 11003-00-2 (Actinin)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Transitional Cell
MH  - *Ureteral Neoplasms/genetics/surgery
MH  - DNA Copy Number Variations/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - *Urinary Bladder Neoplasms
MH  - Biomarkers, Tumor/genetics/analysis
MH  - Prognosis
MH  - *Kidney Neoplasms
MH  - *Urinary Tract/chemistry
MH  - Retrospective Studies
MH  - Actinin/genetics
PMC - PMC10394141
OTO - NOTNLM
OT  - epithelial-mesenchymal transition
OT  - fluorescence in situ hybridization
OT  - upper urinary tract
OT  - urothelial carcinoma
OT  - alpha-actinin4
COIS- The authors have no conflict of interest. Kazufumi Honda is an Associate Editor 
      of Cancer Science.
EDAT- 2023/05/25 06:42
MHDA- 2023/08/03 06:43
PMCR- 2023/05/24
CRDT- 2023/05/25 04:21
PHST- 2023/03/12 00:00 [revised]
PHST- 2022/12/14 00:00 [received]
PHST- 2023/04/25 00:00 [accepted]
PHST- 2023/08/03 06:43 [medline]
PHST- 2023/05/25 06:42 [pubmed]
PHST- 2023/05/25 04:21 [entrez]
PHST- 2023/05/24 00:00 [pmc-release]
AID - CAS15841 [pii]
AID - 10.1111/cas.15841 [doi]
PST - ppublish
SO  - Cancer Sci. 2023 Aug;114(8):3411-3422. doi: 10.1111/cas.15841. Epub 2023 May 24.