Algorithms and Methods for Assessing Late Clinical Endpoints in Prostate Cancer
The present disclosure relates to uses of a multiple gene-expression based Genomic Prostate Score™ (GPS™) algorithm for assessment of various clinical endpoints in prostate cancer patients, such as risks of clinical recurrence (CR), biochemical recurrence (BCR), distant metastasis (Mets), and prostate cancer death (PCD). In some embodiments, GPS result is determined for low and intermediate risk prostate cancer patients in order to assist in determining treatment strategies for those patients.
1 . A method of predicting likelihood of adverse clinical outcome in a prostate cancer patient, comprising:
(a) measuring, in a biological sample containing cancer cells obtained from the patient, levels of RNA transcripts of the following genes: BGN, COLIA1, SFRP4, FLNC, GSN, TPM2, GSTM2, FAM13C, KLK2, AZGP1, SRD5A2, and TPX2;
(b) normalizing the levels of the RNA transcripts of the genes to obtain normalized gene expression levels;
(c) calculating a quantitative score (QS) for the patient, wherein the quantitative score is calculated as follows, wherein the gene symbols below represent the normalized gene expression levels for each respective gene:
(i) calculating an unscaled quantitative score (QSu) as follows:
QSu
=
0.735
*
Stromal
Response
group
score
-
0.368
*
Cellular
Organization
group
score
-
0.352
*
Androgen
group
score
+
0.095
*
Proliferation
group
score
Where
:
The
Stromal
Response
group
score
=
0.527
*
BGN
+
0.457
*
COL
1
A
1
+
0.156
*
SFRP
4
The
Cellular
Organization
group
score
=
0.163
*
FLNC
+
0.504
*
GSN
+
0.421
*
TPM
2
+
0.394
*
GSTM
2
The
Androgen
group
score
=
0.634
*
FAM
13
C
+
1.079
*
KLK
2
+
0.642
*
AZGP
1
+
0.997
*
SRD
5
A
2
Thresh
The
Proliferation
group
score
=
TPX
2
Thresh
where the SRD5A2 Thresh and TPX2 Thresh are calculated via thresholding as follows:
SRD
5
A
2
Thresh
=
{
5.5
if
SRD
5
A
2
<
5.5
SRD
5
A
2
otherwise
TPX
2
Thresh
=
{
5.
if
TPX
2
<
5.
TPX
2
otherwise
(ii) calculating a scaled quantitative score (QS) where:
QS
(
scaled
)
{
0
if
13.4
×
(
QSu
+
10.5
)
>
0
13.4
×
(
QSu
+
10.5
)
if
0
≤
13.4
×
(
QSu
+
10.5
)
≤
100
100
if
13.4
×
(
QSu
+
10.5
)
>
100
(d) assigning the patient to a quantitative score group, wherein (i) the patient is assigned to a lower score group if the patient's QS is either < or ≤a threshold of 38, 39, 40, 41, or 42; and (ii) the patient is assigned to a high score group if the patient's QS is either > or ≥a threshold of 38, 39, 40, 41, or 42; and
(e) predicting a likelihood of adverse clinical outcome for the patient based upon the patient's score group, wherein a lower score group indicates a lower risk of adverse clinical outcome than a high score group.
2 .- 33 . (canceled)