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Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer

Authors
  • Tahkola, Kyösti1, 2
  • Ahtiainen, Maarit1
  • Mecklin, Jukka-Pekka1, 3
  • Kellokumpu, Ilmo1
  • Laukkarinen, Johanna2, 4
  • Tammi, Markku5
  • Tammi, Raija5
  • Väyrynen, Juha P.1, 6
  • Böhm, Jan1
  • 1 Central Finland Health Care District, Jyväskylä, Finland , Jyväskylä (Finland)
  • 2 Tampere University, Tampere, Finland , Tampere (Finland)
  • 3 University of Jyväskylä, Jyväskylä, Finland , Jyväskylä (Finland)
  • 4 Tampere University Hospital, Tampere, Finland , Tampere (Finland)
  • 5 University of Eastern Finland, Kuopio, Finland , Kuopio (Finland)
  • 6 University of Oulu and Oulu University Hospital, Oulu, Finland , Oulu (Finland)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Jun 09, 2021
Volume
11
Issue
1
Identifiers
DOI: 10.1038/s41598-021-91796-x
Source
Springer Nature
License
Green

Abstract

Hyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.

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