LRIG1 and the liar paradox in prostate cancer: A study of the expression and clinical significance of LRIG1 in prostate cancer.
2011 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, no 12, 2843-2852 p.Article in journal (Refereed) Published
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 signalling and a proposed tumour suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In the present 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, tumour 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 U.S. series, high LRIG1 expression was significantly associated with longer 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 upon the clinical and biological circumstances.
Place, publisher, year, edition, pages
Wiley , 2011. Vol. 128, no 12, 2843-2852 p.
LRIG1, prostate cancer, survival
Cancer and Oncology
IdentifiersURN: urn:nbn:se:umu:diva-40756DOI: 10.1002/ijc.25820PubMedID: 21128282OAI: oai:DiVA.org:umu-40756DiVA: diva2:402658