US 12,486,540 B2
Post-surgical risk stratification based on PDE4D variant expression, selected according to TMPRSS2-ERG fusion status, and post-surgical clinical variables
Ralf Dieter Hoffmann, Brueggen (DE)
Assigned to KONINKLIJKE PHILIPS N.V., Eindhoven (NL)
Appl. No. 17/041,534
Filed by KONINKLIJKE PHILIPS N.V., Eindhoven (NL)
PCT Filed Mar. 28, 2019, PCT No. PCT/EP2019/057829
§ 371(c)(1), (2) Date Sep. 25, 2020,
PCT Pub. No. WO2019/185773, PCT Pub. Date Oct. 3, 2019.
Claims priority of application No. 18164842 (EP), filed on Mar. 29, 2018.
Prior Publication US 2021/0025010 A1, Jan. 28, 2021
Int. Cl. C12Q 1/6886 (2018.01)
CPC C12Q 1/6886 (2013.01) [C12Q 2600/112 (2013.01); C12Q 2600/118 (2013.01); C12Q 2600/156 (2013.01); C12Q 2600/158 (2013.01)] 8 Claims
 
1. A method of post-surgical risk stratification of a prostate cancer subject that has previously undergone prostate surgery, comprising:
determining a transmembrane protease, serine 2-ETS-related gene (TMPRSS2-ERG) fusion status in a biological sample obtained from the prostate cancer subject, wherein the determined TMPRSS2-ERG fusion status is either positive or negative,
determining, based on the determined TMPRSS2-ERG fusion status, a gene expression profile for a selected phosphodiesterase 4D variant in a biological sample obtained from the prostate cancer subject, wherein, when the determined TMPRSS2-ERG fusion status is positive the selected phosphodiesterase 4D variant is phosphodiesterase 4D variant 7 (PDE4D7), and when the TMPRSS2-ERG fusion status is negative the selected phosphodiesterase 4D variant is selected to be phosphodiesterase 4D variant 9 (PDE4D9),
determining an expression based risk score for the prostate cancer subject based on the gene expression profile for the selected phosphodiesterase 4D variant,
determining a post-surgical Cancer of the Prostate Risk Assessment (CAPRA-S) score for the prostate cancer subject, wherein the CAPRA-S score comprises the following post-surgical clinical variables of the prostate cancer subject: (i) a prostate-specific antigen (PSA) level; (ii) a pathologic Gleason score (pGS); (iii) surgical margins (SM); (iv) an extracapsular extension (ECE); (v) a seminal vesicle invasion (SVI); and (vi) a lymph node invasion (LNI),
determining a post-surgical prognostic risk score for the prostate cancer subject based on a combination of: (i) the determined expression based risk score and (ii) the determined CAPRA-S score,
stratifying, using the determined post-surgical prognostic risk score for the prostate cancer subject, the prostate cancer subject into a risk group comprising a high risk of disease and disease recurrence after primary treatment, and
administering a post-surgical, secondary prostate cancer treatment to the prostate cancer subject stratified in the risk group, wherein the post-surgical, secondary treatment is selected from the group consisting of: radiation therapy, hormonal therapy, chemotherapy, immunotherapy, or any combination thereof.