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LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer

Thomasson, Marcus ; Wang, Baofeng ; Hammarsten, Peter ; Dahlman, Anna K LU ; Persson, Jenny L LU ; Josefsson, Andreas ; Stattin, Par ; Granfors, Torvald ; Egevad, Lars and Henriksson, Roger , et al. (2011) In International Journal of Cancer 128(12). p.2843-2852
Abstract
The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In our study, the expression of LRIG1 protein in prostate cancer was evaluated for the first time. Immunohistochemistry was performed on tissue microarrays from two different patient series: 355 Swedish patients diagnosed by transurethral resection and 293 American patients who underwent radical prostatectomy. In the Swedish series, high expression of LRIG1 correlated with Gleason score,... (More)
The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In our study, the expression of LRIG1 protein in prostate cancer was evaluated for the first time. Immunohistochemistry was performed on tissue microarrays from two different patient series: 355 Swedish patients diagnosed by transurethral resection and 293 American patients who underwent radical prostatectomy. In the Swedish series, high expression of LRIG1 correlated with Gleason score, T-stage, tumor cell proliferation, vascular density and epidermal growth factor receptor (EGFR) phosphorylation. Among the 256 Swedish patients, followed by watchful waiting, high LRIG1 expression was significantly associated with short overall and prostate cancer-specific survival. In contrast, in the US series, high LRIG1 expression was significantly associated with long overall survival. In vitro cell experiments showed that LRIG1 was induced by androgen stimulation, and its expression inhibited prostate cancer cell proliferation. Thus, LRIG1 expression was an independent marker for poor survival in the untreated patient series, perhaps as a secondary marker of androgen receptor and/or EGFR activation. On the contrary, LRIG1 was a marker for good prognosis after prostatectomy, which might be due to its growth inhibiting properties. We propose that LRIG1 is an important determinant of prostate cancer growth, and the implications of its expression on patient outcome depend on the clinical and biological circumstances. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
LRIG1, prostate cancer, survival
in
International Journal of Cancer
volume
128
issue
12
pages
2843 - 2852
publisher
John Wiley & Sons Inc.
external identifiers
  • wos:000289986900009
  • scopus:79955477797
  • pmid:21128282
ISSN
0020-7136
DOI
10.1002/ijc.25820
language
English
LU publication?
yes
id
d8cc8621-8b14-4985-88ec-48e3607b4347 (old id 1964368)
date added to LUP
2016-04-01 10:13:06
date last changed
2022-04-19 23:52:13
@article{d8cc8621-8b14-4985-88ec-48e3607b4347,
  abstract     = {{The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In our study, the expression of LRIG1 protein in prostate cancer was evaluated for the first time. Immunohistochemistry was performed on tissue microarrays from two different patient series: 355 Swedish patients diagnosed by transurethral resection and 293 American patients who underwent radical prostatectomy. In the Swedish series, high expression of LRIG1 correlated with Gleason score, T-stage, tumor cell proliferation, vascular density and epidermal growth factor receptor (EGFR) phosphorylation. Among the 256 Swedish patients, followed by watchful waiting, high LRIG1 expression was significantly associated with short overall and prostate cancer-specific survival. In contrast, in the US series, high LRIG1 expression was significantly associated with long overall survival. In vitro cell experiments showed that LRIG1 was induced by androgen stimulation, and its expression inhibited prostate cancer cell proliferation. Thus, LRIG1 expression was an independent marker for poor survival in the untreated patient series, perhaps as a secondary marker of androgen receptor and/or EGFR activation. On the contrary, LRIG1 was a marker for good prognosis after prostatectomy, which might be due to its growth inhibiting properties. We propose that LRIG1 is an important determinant of prostate cancer growth, and the implications of its expression on patient outcome depend on the clinical and biological circumstances.}},
  author       = {{Thomasson, Marcus and Wang, Baofeng and Hammarsten, Peter and Dahlman, Anna K and Persson, Jenny L and Josefsson, Andreas and Stattin, Par and Granfors, Torvald and Egevad, Lars and Henriksson, Roger and Bergh, Anders and Hedman, Hakan}},
  issn         = {{0020-7136}},
  keywords     = {{LRIG1; prostate cancer; survival}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{2843--2852}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer}},
  url          = {{http://dx.doi.org/10.1002/ijc.25820}},
  doi          = {{10.1002/ijc.25820}},
  volume       = {{128}},
  year         = {{2011}},
}