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Cholesterol Metabolism and Prostate Cancer Lethality
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, College of Medicine and College of Public Health and Health Professions, University of Florida, Gainesville, Florida.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Statistics, Ohio State University, Columbus, Ohio.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
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2016 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 76, no 16, 4785-4790 p.Article in journal (Refereed) Published
Abstract [en]

Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease.

Place, publisher, year, edition, pages
American Association for Cancer Research Inc. , 2016. Vol. 76, no 16, 4785-4790 p.
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:oru:diva-52692DOI: 10.1158/0008-5472.CAN-16-0903ISI: 000382297700020PubMedID: 27325648ScopusID: 2-s2.0-84982168574OAI: oai:DiVA.org:oru-52692DiVA: diva2:1010226
Available from: 2016-10-03 Created: 2016-09-30 Last updated: 2016-10-03Bibliographically approved

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