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Fibrinogen-like protein 2 in gastrointestinal stromal tumour

Pulkka, Olli Pekka ; Viisanen, Leevi ; Tynninen, Olli ; Laaksonen, Maria ; Reichardt, Peter ; Reichardt, Annette ; Eriksson, Mikael LU orcid ; Hall, Kirsten Sundby ; Wardelmann, Eva and Nilsson, Bengt , et al. (2022) In Journal of Cellular and Molecular Medicine 26(4). p.1083-1094
Abstract

Gastrointestinal stromal tumour (GIST), the most common sarcoma of the gastrointestinal tract, can be treated effectively with tyrosine kinase inhibitors, such as imatinib. Cancer immune therapy has limited efficacy, and little is known about the immune suppressive factors in GISTs. Fibrinogen-like protein 2 (FGL2) is expressed either as a membrane-associated protein or as a secreted soluble protein that has immune suppressive functions. We found that GISTs expressed FGL2 mRNA highly compared to other types of cancer in a large human cancer transcriptome database. GIST expressed FGL2 frequently also when studied using immunohistochemistry in two large clinical series, where 333 (78%) out of the 425 GISTs were FGL2 positive. The... (More)

Gastrointestinal stromal tumour (GIST), the most common sarcoma of the gastrointestinal tract, can be treated effectively with tyrosine kinase inhibitors, such as imatinib. Cancer immune therapy has limited efficacy, and little is known about the immune suppressive factors in GISTs. Fibrinogen-like protein 2 (FGL2) is expressed either as a membrane-associated protein or as a secreted soluble protein that has immune suppressive functions. We found that GISTs expressed FGL2 mRNA highly compared to other types of cancer in a large human cancer transcriptome database. GIST expressed FGL2 frequently also when studied using immunohistochemistry in two large clinical series, where 333 (78%) out of the 425 GISTs were FGL2 positive. The interstitial cells of Cajal, from which GISTs may originate, expressed FGL2. FGL2 expression was associated with small GIST size, low mitotic counts and low tumour-infiltrating lymphocyte (TIL) counts. Patients whose GIST expressed FGL2 had better recurrence-free survival than patients whose GIST lacked expression. Imatinib upregulated FGL2 in GIST cell lines, and the patients with FGL2-negative GIST appeared to benefit most from long duration of adjuvant imatinib. We conclude that GISTs express FGL2 frequently and that FGL2 expression is associated with low TIL counts and favourable survival outcomes.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Cellular and Molecular Medicine
volume
26
issue
4
pages
1083 - 1094
publisher
Wiley-Blackwell
external identifiers
  • scopus:85122766581
  • pmid:35029030
ISSN
1582-1838
DOI
10.1111/jcmm.17163
language
English
LU publication?
yes
id
a2fa3cba-3a9d-4de2-8bd9-21931dcb3572
date added to LUP
2022-02-18 15:24:06
date last changed
2024-04-23 02:04:23
@article{a2fa3cba-3a9d-4de2-8bd9-21931dcb3572,
  abstract     = {{<p>Gastrointestinal stromal tumour (GIST), the most common sarcoma of the gastrointestinal tract, can be treated effectively with tyrosine kinase inhibitors, such as imatinib. Cancer immune therapy has limited efficacy, and little is known about the immune suppressive factors in GISTs. Fibrinogen-like protein 2 (FGL2) is expressed either as a membrane-associated protein or as a secreted soluble protein that has immune suppressive functions. We found that GISTs expressed FGL2 mRNA highly compared to other types of cancer in a large human cancer transcriptome database. GIST expressed FGL2 frequently also when studied using immunohistochemistry in two large clinical series, where 333 (78%) out of the 425 GISTs were FGL2 positive. The interstitial cells of Cajal, from which GISTs may originate, expressed FGL2. FGL2 expression was associated with small GIST size, low mitotic counts and low tumour-infiltrating lymphocyte (TIL) counts. Patients whose GIST expressed FGL2 had better recurrence-free survival than patients whose GIST lacked expression. Imatinib upregulated FGL2 in GIST cell lines, and the patients with FGL2-negative GIST appeared to benefit most from long duration of adjuvant imatinib. We conclude that GISTs express FGL2 frequently and that FGL2 expression is associated with low TIL counts and favourable survival outcomes.</p>}},
  author       = {{Pulkka, Olli Pekka and Viisanen, Leevi and Tynninen, Olli and Laaksonen, Maria and Reichardt, Peter and Reichardt, Annette and Eriksson, Mikael and Hall, Kirsten Sundby and Wardelmann, Eva and Nilsson, Bengt and Sihto, Harri and Joensuu, Heikki}},
  issn         = {{1582-1838}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{1083--1094}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Cellular and Molecular Medicine}},
  title        = {{Fibrinogen-like protein 2 in gastrointestinal stromal tumour}},
  url          = {{http://dx.doi.org/10.1111/jcmm.17163}},
  doi          = {{10.1111/jcmm.17163}},
  volume       = {{26}},
  year         = {{2022}},
}