Gene expression profile algorithm and test for determining prognosis of prostate cancer
View Patent ↗The present invention provides algorithm-based molecular assays that involve measurement of expression levels of genes, or their co-expressed genes, from a biological sample obtained from a prostate cancer patient. The genes may be grouped into functional gene subsets for calculating a quantitative score useful to predict a likelihood of a clinical outcome for a prostate cancer patient.
1. A method of predicting a likelihood of a clinical outcome for a patient with prostate cancer, comprising:
(a) measuring levels of RNA transcripts of the following genes: BGN, COL1A1, SFRP4, FLNC, GSN, TPM2, GSTM2, FAM13C, KLK2, AZGP1, SRD5A2, and TPX2, in a biological sample containing cancer cells obtained from the patient;
(b) normalizing the level of the RNA transcripts to obtain normalized gene expression levels;
(c) calculating a quantitative score for the patient, wherein the quantitative score (QS) is calculated as follows:
QS= 0.735 ×ECM (Stromal Response) group score
−0.368×Migration (Cellular Organization) group score
−0.352×PSA (Androgen) group score
+0.095×Proliferation ( TPX 2) score,
wherein
ECM (Stromal Response) group score=0.527 ×BGN+ 0.457 ×COL 1 A 1+0.156 ×SFRP 4
Migration (Cellular Organization) group score=0.163 ×FLNC+ 0.504 ×GSN+ 0.421 ×TPM 2+0.394 ×GSTM 2
PSA (Androgen) group score=0.634 ×FAM 13 C+ 1.079 ×KLK 2+0.642 ×AZGP 1+0.997 ×SRD 5 A 2 Threshold score
Proliferation ( TPX 2) score= TPX 2 Threshold score,
wherein
SRD
5
A
2
Threshold
Score
=
{
5.5
if
SRD
5
A2
<
5.5
SRD
5
A
2
otherwise
and
TPX
Threshold
Score
=
{
5.0
if
TPX
2
<
5.0
TPX
2
otherwise
,
and
wherein the gene symbols in the equations represent the normalized gene expression levels of the RNA transcripts of the respective genes; and
(d) predicting the likelihood of a clinical outcome for the patient based on the quantitative score.
2. The method of claim 1 , wherein the normalized expression levels of BGN, COL1A1, SFRP4, FLNC, GSN, TPM2, GSTM2, FAM13C, KLK2, AZGP1, SRD5A2, and TPX2 are normalized relative to the expression levels of ARF1, ATP5E, CLTC, GPS1, and PGK1.
3. The method of claim 1 , wherein an increase in the quantitative score correlates with an increased likelihood of a negative clinical outcome.
4. The method of claim 1 , wherein the clinical outcome is upgrading of prostate cancer.
5. The method of claim 1 , wherein the clinical outcome is upstaging of prostate cancer.
6. The method of claim 1 , wherein the clinical outcome is recurrence of prostate cancer.
7. The method of claim 1 , wherein the clinical outcome is non-organ-confined disease.
8. The method of claim 1 , wherein the clinical outcome is adverse pathology.
9. The method of claim 1 , wherein determination of the level of the RNA transcripts includes quantitative polymerase chain reaction.
10. The method of claim 1 , further comprising creating a report summarizing the likelihood of a clinical outcome.
11. The method of claim 1 , wherein the biological sample containing cancer cells is fixed, paraffin-embedded, or fresh, or frozen.
12. The method of claim 1 , further comprising scaling the quantitative score as follows:
Quantitative
Score
(
scaled
)
{
0
if
13.4
×
(
QS
+
10.5
)
<
0
13.4
×
(
QS
+
10.5
)
if
0
≤
13.4
×
(
QS
+
10.5
)
≤
100
100
if
13.4
×
(
QS
+
10.5
)
>
100.
13. The method of claim 12 , wherein the normalized expression levels of BGN, COL1A1, SFRP4, FLNC, GSN, TPM2, GSTM2, FAM13C, KLK2, AZGP1, SRD5A2, and TPX2 are normalized relative to the expression levels of ARF1, ATP5E, CLTC, GPS1, and PGK1.
14. The method of claim 12 , wherein an increase in the quantitative score correlates with an increased likelihood of a negative clinical outcome.
15. The method of claim 12 , wherein the clinical outcome is upgrading of prostate cancer.
16. The method of claim 12 , wherein the clinical outcome is upstaging of prostate cancer.
17. The method of claim 12 , wherein the clinical outcome is recurrence of prostate cancer.
18. The method of claim 12 , wherein the clinical outcome is non-organ-confined disease.
19. The method of claim 12 , wherein the clinical outcome is adverse pathology.
20. The method of claim 12 , wherein determination of the level of the RNA transcripts includes quantitative polymerase chain reaction.
21. The method of claim 12 , further comprising creating a report summarizing the likelihood of a clinical outcome.
22. The method of claim 12 , wherein the biological sample containing cancer cells is fixed, paraffin-embedded, or fresh, or frozen.