Download Prostate Cancer Molecular Subtypes and Biomarkers

Prostate Cancer Molecular Subtypes and Biomarkers*
Biological
Context
Intrinsic
Subtypes
Genomic Relevant
Marker Research Findings
ERG
ERG fusion or over-expression occurs in ~50% of prostate cancer patients, especially from
European ancestry. ERG fusion in high-grade PIN is associated with early onset prostate cancer.1,2,6
ETV1
ETV1 is an oncogene and may contribute to invasive prostate cancer development. It is
associated with aggressive disease and poorer outcome.2,6
ETV4
ETV4 promotes prostate cancer metastasis in response to coactivation of PI3-kinase and
Ras signaling pathways. ETV4 represents a potential target of therapeutic intervention for
metastatic prostate cancer.6,7
ETV5
ETV5 is an oncogene and may contribute to invasive prostate cancer development. It is
associated with aggressive disease and poorer outcome.6
FLI1
FLI1 is an oncogene and may contribute to invasive prostate cancer development. It is
associated with aggressive disease and poorer outcome.6
SPINK1 Over-expression of SPINK1 has been shown to be associated with poor outcome in ERG- prostate
cancer patients, especially in men with African-American ancestry. In vitro studies suggest that
SPINK1 positive prostate cancer growth is sensitive to EGFR inhibitors such as cetuximab.6
B7H3
Immune
Checkpoint
B7-H3 is highly expressed in many solid tumors and not in normal tissue. In prostate cancer,
over-expression of B7H3 is associated with the development of aggressive prostate cancer
and metastatic disease. B7-H3 expression increases in response to hormone therapy and
inhibition of B7-H3 may be useful for treating hormone resistant prostate cancer.2,11
PDL1/ PD-L1/PD-1-mediated T cell coinhibition is involved in immune evasion in prostate cancer.
immune
PD-1 Over-expression of PDL1 and PD-1 by cancer cells may enable tumors to evade T cell
responses. Over-expression is correlated to greater responses to anti-PD1 therapy.12
Androgen
Signaling
AR
Lower expression of AR is correlated to poor response to hormonal therapy and associated
with neuroendocrine prostate cancer.1
PSA
Lower expression of PSA/KLK3 in prostate tumors is correlated to poor response to hormonal
therapy and associated with neuroendocrine prostate cancer.2
PCA3
PCA3 over-expression is associated with advanced pathologic stage.1,2,7
NKX3-1
NKX3-1 (8p21) is an androgen-responsive transcription factor that functions as a tumor
suppressor gene. It’s expression is absent or at low-levels in many high-grade prostate
cancers and completely lost in the majority of metastatic prostate cancer.1
*Research Use Only
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Prostate Cancer Molecular Subtypes and Biomarkers*
Biological Genomic Relevant
Context
Marker Research Findings
Metastasis
& Invasion
SChLAP1 SChLAP1 is a regulator of cell migration and invasion. Overexpression is associated with
more aggressive prostate cancer, especially in the subset of ERG positive tumors.3,4
SPARCL1 SPARCL1 is a regulator of cell migration/invasion. Its loss is independently associated with
prostate cancer recurrence.5
Ki67
Proliferation
Small Cell
/ Neuroendocrine
Ki-67 is a cell proliferation marker. Overexpression has been shown to be associated with
increased risk of metastasis and prostate cancer death.1,2
TOP2A
TOP2A is a cell proliferation marker and high expression is correlated to poor outcome in prostate
cancer. Patients with TOP2A over-expression may be sensitive to etoposide chemotherapy.1,2
NEAT1
High NEAT1 expression is associated with prostate cancer progression and resistance to AR
antagonists.8
Cyclin
D1
Cyclin D1 loss is common in small cell carcinoma, which are resistant to hormone blockade. In
men with prostate adenocarcinoma who were treated with hormonal therapy, lower cyclin D1
gene expression was associated with more rapid onset of metastasis and death.9
pRB/
RB1
Loss of RB1 by deletion is a common event in prostatic small cell carcinoma. Under-expression
in prostatic adenocarcinoma may be associated with a neuroendocrine phenotype and
resistance to hormonal therapy.1,10
Chromo- Chromogranin is a marker of neurendocrine prostate cancer. Tumors with higher chromogranin A
granin A expression may be less sensitive to hormonal therapy.2
Additional markers continually added, contact us for the most current listing.
References
1. Yamoah, et al. Novel biomarker signature that may predict aggressive disease in African-American men with prostate cancer. Journal of Clinical Oncology, 2015;
DOI: 10.1200/JCO.2014.59.8912.
2. Erho, N., et al., Discovery and Validation of a Prostate Cancer Genomic Classifier that Predicts Early Metastasis Following Radical Prostatectomy. PLoS One.
2013 Jun 24;8(6):e66855.
3. Prensner, et al. RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1,Lancet
Oncology, 2014, 15(13):1469-80.
4. Prensner, et al. The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex. Nature Genetics, 2013, 45(11):1392-8.
5. Hurley, et al., Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical
outcome. PNAS, 2012, 109(37):14977-82.
6. Tomlins, et al. Characterization of 1577 Primary Prostate Cancers Reveals Novel Biological and Clinicopathologic Insights into Molecular Subtypes. European
Urology, 2015, doi: 10.1016/j.eururo.2015.04.033.
7. Aytes, et al. ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer. PNAS, 2013,110(37):E3506-15.
8. Chakravaty, et al. The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer. Nature Comm, 2014, 21;5:5383.
9. Tsai, et al., Cyclin D1 Loss Distinguishes Prostatic Small Cell Carcinoma from Most Prostatic Adenocarcinomas. Clinical Cancer Research. doi:10.1158/1078-0432.CCR-15-0744.
10. Tan,et al., Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma. Clinical Cancer Research, 2014, 20(4):890-903.
11. Chavin, et al. Expression of immunosuppresive B7-H3 ligand by hormone-treated prostate cancer tumors and metastases. Clinical Cancer Research, 2009,15(6):2174-80.
12. Zitvogel and Kroemer, Targeting PD-1/PD-L1 interactions for immunotherapy. Oncoimmunology, 2012,1(8):1223-1225.
*Research Use Only
To learn more about Decipher GRID™,
visit DecipherGRID.com or call 1.888.792.1601.
Copyright © 2015 GenomeDx Biosciences Inc.
Join the conversation #InTheGRID
(2/2)