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Low P4HA2 and high PRTN3 expression predicts poor survival in patients with pancreatic cancer

Hu, Dingyuan LU ; Ansari, Daniel LU ; Zhou, Qimin LU orcid ; Sasor, Agata LU ; Hilmersson, Katarzyna Said LU and Andersson, Roland LU (2019) In Scandinavian Journal of Gastroenterology 54(2). p.246-251
Abstract

Background: The tumor microenvironment in pancreatic cancer has a multifaceted role in disease development and progression. Prolyl 4-hydroxylase subunit alpha 2 (P4HA2) and proteinase 3 (PRTN3) are involved in the synthesis and degradation of collagen in the tumor microenvironment and have been identified as prognostic biomarker candidates for pancreatic cancer in our previous mass spectro-metric study. This study aimed at validating prognostic performance of P4HA2 and PRTN3 in a larger cohort of patients. Methods: The expression of P4HA2 and PRTN3 was evaluated with tissue microarrays and immunohis-tochemistry in 140 patients with pancreatic cancer who underwent surgical resection. Kaplan–Meier and Cox proportional hazards regression... (More)

Background: The tumor microenvironment in pancreatic cancer has a multifaceted role in disease development and progression. Prolyl 4-hydroxylase subunit alpha 2 (P4HA2) and proteinase 3 (PRTN3) are involved in the synthesis and degradation of collagen in the tumor microenvironment and have been identified as prognostic biomarker candidates for pancreatic cancer in our previous mass spectro-metric study. This study aimed at validating prognostic performance of P4HA2 and PRTN3 in a larger cohort of patients. Methods: The expression of P4HA2 and PRTN3 was evaluated with tissue microarrays and immunohis-tochemistry in 140 patients with pancreatic cancer who underwent surgical resection. Kaplan–Meier and Cox proportional hazards regression modeling were used to explore the association of P4HA2 and PRTN3, either separately or combined, with clinicopathological factors and survival. Results: Most tumors were positive for P4HA2 (133/140, 95%), whereas 77 tumors (55%) were positive for PRTN3. Expression levels of P4HA2 and PRTN3 did not separately correlate with disease-free or overall survival, in either uni-or multivariable analysis. However, a low P4HA2 and high PRTN3 expression correlated with shorter disease-free survival (median 7.0 vs. 13.4 months, adjusted HR 3.24, 95% CI: 1.13–9.25, p ¼.028) and overall survival (median 8.5 vs. 25.8 months, adjusted HR 8.14, 95% CI: 3.41–19.44, p <.001). Conclusion: Our data show that a low P4HA2 and high PRTN3 expression correlates with poor survival in patients with pancreatic cancer, indicating the involvement of collagen deposition in the restraint of the tumor. The tumoral expression of PRTN3 reinforces the therapeutic potential of PR1-targeting immunotherapy in pancreatic cancer.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Pancreatic cancer, Prolyl 4-hydroxylase subunit alpha 2, Proteinase 3, Survival
in
Scandinavian Journal of Gastroenterology
volume
54
issue
2
pages
6 pages
publisher
Taylor & Francis
external identifiers
  • pmid:30880498
  • scopus:85063936574
ISSN
0036-5521
DOI
10.1080/00365521.2019.1574360
language
English
LU publication?
yes
additional info
Export Date: 27 January 2020
id
149f9ee1-cea9-4a38-9d51-d16568e180ef
alternative location
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85063936574&doi=10.1080%2f00365521.2019.1574360&partnerID=40&md5=ccbe992efb94ff0a7d224b87a3e5d060
date added to LUP
2019-05-08 12:22:42
date last changed
2024-04-16 03:54:36
@article{149f9ee1-cea9-4a38-9d51-d16568e180ef,
  abstract     = {{<p>Background: The tumor microenvironment in pancreatic cancer has a multifaceted role in disease development and progression. Prolyl 4-hydroxylase subunit alpha 2 (P4HA2) and proteinase 3 (PRTN3) are involved in the synthesis and degradation of collagen in the tumor microenvironment and have been identified as prognostic biomarker candidates for pancreatic cancer in our previous mass spectro-metric study. This study aimed at validating prognostic performance of P4HA2 and PRTN3 in a larger cohort of patients. Methods: The expression of P4HA2 and PRTN3 was evaluated with tissue microarrays and immunohis-tochemistry in 140 patients with pancreatic cancer who underwent surgical resection. Kaplan–Meier and Cox proportional hazards regression modeling were used to explore the association of P4HA2 and PRTN3, either separately or combined, with clinicopathological factors and survival. Results: Most tumors were positive for P4HA2 (133/140, 95%), whereas 77 tumors (55%) were positive for PRTN3. Expression levels of P4HA2 and PRTN3 did not separately correlate with disease-free or overall survival, in either uni-or multivariable analysis. However, a low P4HA2 and high PRTN3 expression correlated with shorter disease-free survival (median 7.0 vs. 13.4 months, adjusted HR 3.24, 95% CI: 1.13–9.25, p ¼.028) and overall survival (median 8.5 vs. 25.8 months, adjusted HR 8.14, 95% CI: 3.41–19.44, p &lt;.001). Conclusion: Our data show that a low P4HA2 and high PRTN3 expression correlates with poor survival in patients with pancreatic cancer, indicating the involvement of collagen deposition in the restraint of the tumor. The tumoral expression of PRTN3 reinforces the therapeutic potential of PR1-targeting immunotherapy in pancreatic cancer.</p>}},
  author       = {{Hu, Dingyuan and Ansari, Daniel and Zhou, Qimin and Sasor, Agata and Hilmersson, Katarzyna Said and Andersson, Roland}},
  issn         = {{0036-5521}},
  keywords     = {{Pancreatic cancer; Prolyl 4-hydroxylase subunit alpha 2; Proteinase 3; Survival}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{246--251}},
  publisher    = {{Taylor & Francis}},
  series       = {{Scandinavian Journal of Gastroenterology}},
  title        = {{Low P4HA2 and high PRTN3 expression predicts poor survival in patients with pancreatic cancer}},
  url          = {{http://dx.doi.org/10.1080/00365521.2019.1574360}},
  doi          = {{10.1080/00365521.2019.1574360}},
  volume       = {{54}},
  year         = {{2019}},
}