Cholesterol metabolism and prostate cancer lethality

Konrad H. Stopsack, Travis A. Gerke, Jennifer A. Sinnott, Kathryn L. Penney, Svitlana Tyekucheva, Howard D. Sesso, Swen Olof Andersson, Ove Andrén, James R Cerhan, Edward L. Giovannucci, Lorelei A. Mucci, Jennifer R. Rider

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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. Cancer Res; 76(16); 4785-90.

Original languageEnglish (US)
Pages (from-to)4785-4790
Number of pages6
JournalCancer Research
Volume76
Issue number16
DOIs
StatePublished - Aug 15 2016

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Squalene Monooxygenase
Prostatic Neoplasms
Cholesterol
Neoplasms
Watchful Waiting
Neoplasm Metastasis
Health
Enzymes
Prostatectomy
Prostate
Confidence Intervals
Physicians

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Stopsack, K. H., Gerke, T. A., Sinnott, J. A., Penney, K. L., Tyekucheva, S., Sesso, H. D., ... Rider, J. R. (2016). Cholesterol metabolism and prostate cancer lethality. Cancer Research, 76(16), 4785-4790. https://doi.org/10.1158/0008-5472.CAN-16-0903

Cholesterol metabolism and prostate cancer lethality. / Stopsack, Konrad H.; Gerke, Travis A.; Sinnott, Jennifer A.; Penney, Kathryn L.; Tyekucheva, Svitlana; Sesso, Howard D.; Andersson, Swen Olof; Andrén, Ove; Cerhan, James R; Giovannucci, Edward L.; Mucci, Lorelei A.; Rider, Jennifer R.

In: Cancer Research, Vol. 76, No. 16, 15.08.2016, p. 4785-4790.

Research output: Contribution to journalArticle

Stopsack, KH, Gerke, TA, Sinnott, JA, Penney, KL, Tyekucheva, S, Sesso, HD, Andersson, SO, Andrén, O, Cerhan, JR, Giovannucci, EL, Mucci, LA & Rider, JR 2016, 'Cholesterol metabolism and prostate cancer lethality', Cancer Research, vol. 76, no. 16, pp. 4785-4790. https://doi.org/10.1158/0008-5472.CAN-16-0903
Stopsack KH, Gerke TA, Sinnott JA, Penney KL, Tyekucheva S, Sesso HD et al. Cholesterol metabolism and prostate cancer lethality. Cancer Research. 2016 Aug 15;76(16):4785-4790. https://doi.org/10.1158/0008-5472.CAN-16-0903
Stopsack, Konrad H. ; Gerke, Travis A. ; Sinnott, Jennifer A. ; Penney, Kathryn L. ; Tyekucheva, Svitlana ; Sesso, Howard D. ; Andersson, Swen Olof ; Andrén, Ove ; Cerhan, James R ; Giovannucci, Edward L. ; Mucci, Lorelei A. ; Rider, Jennifer R. / Cholesterol metabolism and prostate cancer lethality. In: Cancer Research. 2016 ; Vol. 76, No. 16. pp. 4785-4790.
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