Association of High miR-182 Levels with Low-Risk Prostate Cancer

Bethany Baumann, Andrés M. Acosta, Zachary Richards, Ryan Deaton, Anastasiya Sapatynska, Adam Murphy, Andre Kajdacsy-Balla, Peter H. Gann, Larisa Nonn*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium. miR-182 was significantly higher in cancer epithelium than adjacent benign epithelium (P < 0.0001). The ratio of cancer to benign miR-182 expression per patient was inversely associated with recurrence in a multivariate logistic regression model (odds ratio = 0.18; 95% CI, 0.03–0.89; P = 0.044). Correlation of miR-182 with mRNA expression in laser-capture microdissected benign prostate epithelium was used to predict prostatic miR-182 targets. Genes that were negatively correlated with miR-182 were enriched for its predicted targets and for genes previously identified as up-regulated in prostate cancer metastases. miR-182 expression was also negatively correlated with genes previously identified as up-regulated in primary prostate tumors from African American patients, who are at an increased risk of developing aggressive prostate cancer. Taken together, these results suggest that although miR-182 is expressed at higher levels in localized prostate cancer, its levels are lower in aggressive cancers, suggesting a biphasic role for this miRNA that may be exploited for prognostic and/or therapeutic purposes to reduce prostate cancer progression.

Original languageEnglish (US)
Pages (from-to)911-923
Number of pages13
JournalAmerican Journal of Pathology
Volume189
Issue number4
DOIs
StatePublished - Apr 2019

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Prostate
Prostatic Neoplasms
Epithelium
MicroRNAs
Neoplasms
Logistic Models
Genes
Laser Capture Microdissection
Recurrence
African Americans
In Situ Hybridization
Lasers
Odds Ratio
Neoplasm Metastasis
Messenger RNA
Therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Baumann, B., Acosta, A. M., Richards, Z., Deaton, R., Sapatynska, A., Murphy, A., ... Nonn, L. (2019). Association of High miR-182 Levels with Low-Risk Prostate Cancer. American Journal of Pathology, 189(4), 911-923. https://doi.org/10.1016/j.ajpath.2018.12.014
Baumann, Bethany ; Acosta, Andrés M. ; Richards, Zachary ; Deaton, Ryan ; Sapatynska, Anastasiya ; Murphy, Adam ; Kajdacsy-Balla, Andre ; Gann, Peter H. ; Nonn, Larisa. / Association of High miR-182 Levels with Low-Risk Prostate Cancer. In: American Journal of Pathology. 2019 ; Vol. 189, No. 4. pp. 911-923.
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abstract = "A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium. miR-182 was significantly higher in cancer epithelium than adjacent benign epithelium (P < 0.0001). The ratio of cancer to benign miR-182 expression per patient was inversely associated with recurrence in a multivariate logistic regression model (odds ratio = 0.18; 95{\%} CI, 0.03–0.89; P = 0.044). Correlation of miR-182 with mRNA expression in laser-capture microdissected benign prostate epithelium was used to predict prostatic miR-182 targets. Genes that were negatively correlated with miR-182 were enriched for its predicted targets and for genes previously identified as up-regulated in prostate cancer metastases. miR-182 expression was also negatively correlated with genes previously identified as up-regulated in primary prostate tumors from African American patients, who are at an increased risk of developing aggressive prostate cancer. Taken together, these results suggest that although miR-182 is expressed at higher levels in localized prostate cancer, its levels are lower in aggressive cancers, suggesting a biphasic role for this miRNA that may be exploited for prognostic and/or therapeutic purposes to reduce prostate cancer progression.",
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Baumann, B, Acosta, AM, Richards, Z, Deaton, R, Sapatynska, A, Murphy, A, Kajdacsy-Balla, A, Gann, PH & Nonn, L 2019, 'Association of High miR-182 Levels with Low-Risk Prostate Cancer', American Journal of Pathology, vol. 189, no. 4, pp. 911-923. https://doi.org/10.1016/j.ajpath.2018.12.014

Association of High miR-182 Levels with Low-Risk Prostate Cancer. / Baumann, Bethany; Acosta, Andrés M.; Richards, Zachary; Deaton, Ryan; Sapatynska, Anastasiya; Murphy, Adam; Kajdacsy-Balla, Andre; Gann, Peter H.; Nonn, Larisa.

In: American Journal of Pathology, Vol. 189, No. 4, 04.2019, p. 911-923.

Research output: Contribution to journalArticle

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T1 - Association of High miR-182 Levels with Low-Risk Prostate Cancer

AU - Baumann, Bethany

AU - Acosta, Andrés M.

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AU - Deaton, Ryan

AU - Sapatynska, Anastasiya

AU - Murphy, Adam

AU - Kajdacsy-Balla, Andre

AU - Gann, Peter H.

AU - Nonn, Larisa

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