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Nuclear ubiquitin C-terminal hydrolase L5 expression associates with increased patient survival in pancreatic ductal adenocarcinoma.

Abstract Pancreatic ductal adenocarcinoma is a lethal disease with an overall 5-year survival of less than 5%. Prognosis among surgically treated patients is difficult and identification of new biomarkers is essential for accurate prediction of patient outcome. As part of one of the major cellular protein degradation systems, the proteasome plays a fundamental role in both physiological and pathophysiological conditions including cancer. The proteasome-associated deubiquitinating enzyme ubiquitin C-terminal hydrolase L5 (UCHL5)/Uch37 is a modulator of proteasome activity with cancer prognostic marker potential. Cytoplasmic and nuclear immunoexpression of UCHL5 was evaluated in 154 surgical specimens from pancreatic ductal adenocarcinoma patients treated at Helsinki University Hospital, Finland, in 2000-2011. UCHL5 expression in relation to clinicopathological parameters and the association between UCHL5 In this study, positive expression and patient survival were assessed. Positive nuclear UCHL5 expression was associated with increased patient survival ( p = 0.005). A survival benefit was also detectable in these subgroups of patients: over 65 years ( p < 0.001), at tumor stages IIB to III ( p = 0.007), or with lymph-node positivity ( p = 0.006). In stages IIB to III disease, patients with positive nuclear UCHL5 expression showed a twofold increase in 5-year cancer-specific survival compared to those with negative expression. Multivariate analysis identified positive nuclear UCHL5 expression as an independent prognostic factor ( p = 0.012). In conclusion, UCHL5 expression could function as a prognostic marker in pancreatic ductal adenocarcinoma, particularly at disease stages IIB to III. As UCHL5 is one of the few markers predicting increased survival, our results may be of clinical relevance.
PMID
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Authors

Mayor MeshTerms
Keywords

Deubiquitination

UCHL5

pancreatic ductal adenocarcinoma

prognosis

proteasome

ubiquitin C-terminal hydrolase L5

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28653876
OWN - NLM
STAT- MEDLINE
DA  - 20170627
DCOM- 20170711
LR  - 20170713
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 6
DP  - 2017 Jun
TI  - Nuclear ubiquitin C-terminal hydrolase L5 expression associates with increased
      patient survival in pancreatic ductal adenocarcinoma.
PG  - 1010428317710411
LID - 10.1177/1010428317710411 [doi]
AB  - Pancreatic ductal adenocarcinoma is a lethal disease with an overall 5-year
      survival of less than 5%. Prognosis among surgically treated patients is
      difficult and identification of new biomarkers is essential for accurate
      prediction of patient outcome. As part of one of the major cellular protein
      degradation systems, the proteasome plays a fundamental role in both
      physiological and pathophysiological conditions including cancer. The
      proteasome-associated deubiquitinating enzyme ubiquitin C-terminal hydrolase L5
      (UCHL5)/Uch37 is a modulator of proteasome activity with cancer prognostic marker
      potential. Cytoplasmic and nuclear immunoexpression of UCHL5 was evaluated in 154
      surgical specimens from pancreatic ductal adenocarcinoma patients treated at
      Helsinki University Hospital, Finland, in 2000-2011. UCHL5 expression in relation
      to clinicopathological parameters and the association between UCHL5 In this
      study, positive expression and patient survival were assessed. Positive nuclear
      UCHL5 expression was associated with increased patient survival ( p = 0.005). A
      survival benefit was also detectable in these subgroups of patients: over 65
      years ( p &lt; 0.001), at tumor stages IIB to III ( p = 0.007), or with lymph-node
      positivity ( p = 0.006). In stages IIB to III disease, patients with positive
      nuclear UCHL5 expression showed a twofold increase in 5-year cancer-specific
      survival compared to those with negative expression. Multivariate analysis
      identified positive nuclear UCHL5 expression as an independent prognostic factor 
      ( p = 0.012). In conclusion, UCHL5 expression could function as a prognostic
      marker in pancreatic ductal adenocarcinoma, particularly at disease stages IIB to
      III. As UCHL5 is one of the few markers predicting increased survival, our
      results may be of clinical relevance.
FAU - Arpalahti, Leena
AU  - Arpalahti L
AD  - 1 Research Programs Unit, Translational Cancer Biology Program, University of
      Helsinki, Helsinki, Finland.
FAU - Saukkonen, Kapo
AU  - Saukkonen K
AD  - 1 Research Programs Unit, Translational Cancer Biology Program, University of
      Helsinki, Helsinki, Finland.
AD  - 2 Department of Surgery, University of Helsinki and Helsinki University Hospital,
      Helsinki, Finland.
FAU - Hagstrom, Jaana
AU  - Hagstrom J
AD  - 1 Research Programs Unit, Translational Cancer Biology Program, University of
      Helsinki, Helsinki, Finland.
AD  - 3 Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki 
      and Helsinki University Hospital, Helsinki, Finland.
FAU - Mustonen, Harri
AU  - Mustonen H
AD  - 2 Department of Surgery, University of Helsinki and Helsinki University Hospital,
      Helsinki, Finland.
FAU - Seppanen, Hanna
AU  - Seppanen H
AD  - 2 Department of Surgery, University of Helsinki and Helsinki University Hospital,
      Helsinki, Finland.
FAU - Haglund, Caj
AU  - Haglund C
AD  - 1 Research Programs Unit, Translational Cancer Biology Program, University of
      Helsinki, Helsinki, Finland.
AD  - 2 Department of Surgery, University of Helsinki and Helsinki University Hospital,
      Helsinki, Finland.
FAU - Holmberg, Carina I
AU  - Holmberg CI
AD  - 1 Research Programs Unit, Translational Cancer Biology Program, University of
      Helsinki, Helsinki, Finland.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Biomarkers, Tumor)
RN  - EC 3.4.19.12 (UCHL5 protein, human)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
SB  - IM
MH  - Adenocarcinoma/*genetics/pathology/surgery
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*biosynthesis/genetics
MH  - Carcinoma, Pancreatic Ductal/*genetics/pathology/surgery
MH  - Disease-Free Survival
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Ubiquitin Thiolesterase/*biosynthesis/genetics
OTO - NOTNLM
OT  - Deubiquitination
OT  - UCHL5
OT  - pancreatic ductal adenocarcinoma
OT  - prognosis
OT  - proteasome
OT  - ubiquitin C-terminal hydrolase L5
EDAT- 2017/06/28 06:00
MHDA- 2017/07/14 06:00
CRDT- 2017/06/28 06:00
AID - 10.1177/1010428317710411 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Jun;39(6):1010428317710411. doi: 10.1177/1010428317710411.