Post-surgical risk stratification based on pde4d variant expression, selected according to tmprss2-erg fusion status, and post-surgical clinical variables

A risk stratification, post-operative technique, applied in the fields of biochemical equipment and methods, microbial assay/test, etc., which can solve problems such as side effects

Pending Publication Date: 2020-11-17
KONINKLJIJKE PHILIPS NV
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Problems solved by technology

However, because this treatment has significant side effects, it should only be used in patients who really need this aggressive therapy to prevent disease progression and ultimately prostate cancer-related death

Method used

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  • Post-surgical risk stratification based on pde4d variant expression, selected according to tmprss2-erg fusion status, and post-surgical clinical variables
  • Post-surgical risk stratification based on pde4d variant expression, selected according to tmprss2-erg fusion status, and post-surgical clinical variables
  • Post-surgical risk stratification based on pde4d variant expression, selected according to tmprss2-erg fusion status, and post-surgical clinical variables

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Experimental program
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Embodiment

[0147] Patient Cohorts and Samples

[0148] A cohort of radical prostatectomy (RP) patients was used, whose demographic data are shown in Table 2. A small forceps biopsy sample (approximately 1 mm × 2 mm) representative of the tumor area was collected from the resected prostate from 656 patients who were operated on consecutively between 2000 and 2004 at a large clinical center in Germany . Of the 656 patients, 600 were selected for RNA next-generation sequencing based on the quality and concentration of RNA in the samples after nucleic acid extraction. After quality control of the RNAseq data, 575 patient samples were found to be eligible for statistical analysis.

[0149] Table 2: Demographics of the Radical Prostatectomy (RP) Patient Cohort

[0150]

[0151] Patient age, preoperative PSA, percentage tumor in biopsy, prostate volume, and PSA density are shown in the table, with minimum and maximum values ​​in the cohort, and medians are shown in parentheses. For CAPRA-S...

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Abstract

The invention relates to a method of post-surgical risk stratification of a prostate cancer subject, comprising determining a transmembrane protease, serine 2-ETS-related gene (TMPRSS2-ERG) fusion status in a biological sample obtained from the subject, determining a gene expression profile for each of one or more phosphodiesterase 4D variants in a biological sample obtained from the subject, determining an expression based risk score for the subject based on the gene expression profile for a selected phosphodiesterase 4D variant, and determining a post-surgical prognostic risk score for the subject based on the expression based risk score and post-surgical clinical variables of the subject, wherein the selected phosphodiesterase 4D variant is selected depending on the TMPRSS2-ERG fusion status. This may allow for an improved stratification of the subject in a post-surgical setting that may result in better post-surgical, secondary treatment decisions.

Description

[0001] field of invention [0002] The present invention relates to a method for postoperative risk stratification of prostate cancer subjects. Furthermore, the present invention relates to a diagnostic kit, to the use of said kit in a method for postoperative risk stratification of prostate cancer subjects, to the use of gene expression profiles of phosphodiesterase 4D variants in postoperative risk stratification of prostate cancer subjects , and related computer program products. [0003] Background of the invention [0004] Cancer is a class of diseases in which a group of cells exhibits uncontrolled growth, invasion and sometimes metastasis. These three malignant properties of cancer distinguish it from benign tumors, which are self-limited and do not invade or metastasize. Prostate cancer (PCa) is the most common non-cutaneous malignancy in men. It appears to be a heterogeneous disease with various potentials to progress to lethal forms of the disease. Of the estimate...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/112C12Q2600/118C12Q2600/156C12Q2600/158
Inventor R·D·霍夫曼
Owner KONINKLJIJKE PHILIPS NV
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