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J Natl Cancer Inst. 2014 Oct 8;106(11). pii: dju306. doi: 10.1093/jnci/dju306. Print 2014 Nov.

The Thoc1 ribonucleoprotein and prostate cancer progression.

Author information

1
Department of Pharmacology & Therapeutics (MC, YW, XZ, BAF, DWG), Department of Biostatistics (DLG), Department of Pathology (TK, WB, CDM), Department of Cancer Prevention and Population Science (RDPO), Department of Urology (JLM), Roswell Park Cancer Institute, Buffalo, NY; Department of Biomedical Sciences, Cornell University, Ithaca, NY (AYN); Department of Pathology, Virginia Commonwealth University, Richmond, VA (YL). Current affiliation: MedImmune LLC, Gaitherburg, MD.
2
Current affiliation: MedImmune LLC, Gaitherburg, MD.
3
Department of Pharmacology & Therapeutics (MC, YW, XZ, BAF, DWG), Department of Biostatistics (DLG), Department of Pathology (TK, WB, CDM), Department of Cancer Prevention and Population Science (RDPO), Department of Urology (JLM), Roswell Park Cancer Institute, Buffalo, NY; Department of Biomedical Sciences, Cornell University, Ithaca, NY (AYN); Department of Pathology, Virginia Commonwealth University, Richmond, VA (YL). Current affiliation: MedImmune LLC, Gaitherburg, MD. david.goodrich@roswellpark.org.

Abstract

BACKGROUND:

The majority of newly diagnosed prostate cancers will remain indolent, but distinguishing between aggressive and indolent disease is imprecise. This has led to the important clinical problem of overtreatment. THOC1 encodes a nuclear ribonucleoprotein whose expression is higher in some cancers than in normal tissue. The hypothesis that THOC1 may be a functionally relevant biomarker that can improve the identification of aggressive prostate cancer has not been tested.

METHODS:

THOC1 protein immunostaining was evaluated in a retrospective collection of more than 700 human prostate cancer specimens and the results associated with clinical variables and outcome. Thoc1 was conditionally deleted in an autochthonous mouse model (n = 22 or 23 per genotype) to test whether it is required for prostate cancer progression. All statistical tests were two-sided.

RESULTS:

THOC1 protein immunostaining increases with higher Gleason score and more advanced Tumor/Node/Metastasis stage. Time to biochemical recurrence is statistically significantly shorter for cancers with high THOC1 protein (log-rank P = .002, and it remains statistically significantly associated with biochemical recurrence after adjusting for Gleason score, clinical stage, and prostate-specific antigen levels (hazard ratio = 1.61, 95% confidence interval = 1.03 to 2.51, P = .04). Thoc1 deletion prevents prostate cancer progression in mice, but has little effect on normal tissue. Prostate cancer cells deprived of Thoc1 show gene expression defects that compromise cell growth.

CONCLUSIONS:

Thoc1 is required to support the unique gene expression requirements of aggressive prostate cancer in mice. In humans, high THOC1 protein immunostaining associates with prostate cancer aggressiveness and recurrence. Thus, THOC1 protein is a functionally relevant molecular marker that may improve the identification of aggressive prostate cancers, potentially reducing overtreatment.

PMID:
25296641
PMCID:
PMC4271031
DOI:
10.1093/jnci/dju306
[Indexed for MEDLINE]
Free PMC Article

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