Markers for the diagnosis of biochemical recurrence in prostate cancer
Inventors
Kiebish, Michael Andrew • Narain, Niven Rajin • Sarangarajan, Rangaprasad • Akmaev, Viatcheslav R. • Rodrigues, Leonardo • Zhang, Lixia • Milliman, Eric • Srivastava, Shiv • Dobi, Albert • Cullen, Jennifer
Assignees
Henry M Jackson Foundation for Advancedment of Military Medicine Inc • BPGbio Inc
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Publication Number
US-12320812-B2
Publication Date
2025-06-03
Expiration Date
Abstract
Methods for diagnosing the presence of BCR in prostate cancer in a subject are provided, such methods including the detection of levels of a variety of biomarkers diagnostic of BCR. Compositions in the form of kits and panels of reagents for detecting the biomarkers of the invention are also provided.
Core Innovation
The disclosed subject matter relates to biomarkers and diagnostic use for prostate cancer biochemical recurrence (BCR). The invention describes detection of at least one BCR marker in a biological sample, including blood, serum, plasma, urine, and prostate tissue or biopsy tissue, and comparison of detected levels to predetermined thresholds to diagnose or predict BCR. The markers include phosphatidic acid PA-18:0/22:0, tenascin C, apolipoprotein A-IV, and 1-methyladenosine.
The invention further links the identified biomarker levels with clinical variables for prognostic or risk stratification purposes. Associations are described with tumor stage, including T3/T4, and Gleason score to support disease profiling. Performance metrics are provided, including combined ROC/AUC values and an example combined biomarker plus tumor stage/Gleason AUC=0.89 and OR=12.47.
The disclosure additionally describes measurement and sample coverage for detecting the biomarkers and forming diagnostic signatures. Measurement modalities include mass spectrometry, immunoassays/ELISA, HPLC/UV-Vis spectroscopy, and mRNA detection. The disclosure also covers kit and panel concepts for detecting the biomarkers.
Claims Coverage
Two independent claims are identified. Each claim defines detecting one or more BCR markers including phosphatidic acid-18:0/22:0, comparing detected levels to a predetermined threshold value or comparing levels across time, and administering an anti-cancer therapy selected from specified salvage options.
Threshold-based diagnosis using phosphatidic acid-18:0/22:0 in blood, serum, or plasma for treating BCR
Detecting the level of at least one BCR marker comprising phosphatidic acid-18:0/22:0 in a biological sample selected from blood, serum and plasma; comparing the detected level with a corresponding predetermined threshold value where a lower detected level indicates a diagnosis that BCR is present; and administering a therapeutic anti-cancer treatment selected from salvage radiation therapy, salvage prostatectomy, and androgen deprivation therapy to the subject diagnosed with BCR.
Longitudinal monitoring of BCR progression using phosphatidic acid-18:0/22:0 and treatment based on level comparison
Detecting a first level of at least one BCR marker comprising phosphatidic acid-18:0/22:0 in a first biological sample obtained at a first time; detecting a second level of the at least one BCR marker in a second biological sample obtained at a second time later than the first, with both samples selected from blood, serum and plasma; comparing the first level and the second level where a lower second level compared to the first level indicates progression of BCR; and administering a therapeutic anti-cancer treatment selected from salvage radiation therapy, salvage prostatectomy, and androgen deprivation therapy to the subject indicated as having progression of BCR.
Across the independent claims, the coverage centers on BCR marker detection incorporating phosphatidic acid-18:0/22:0, using either a predetermined threshold comparison for diagnosis or a longitudinal level comparison to indicate progression, followed by selection of salvage radiation therapy, salvage prostatectomy, or androgen deprivation therapy.
Stated Advantages
The biomarker levels are differentially regulated in BCR patients versus controls.
Combined biomarker plus tumor stage/Gleason performance is reported with AUC=0.89 and OR=12.47.
Documented Applications
Diagnosis or prediction of biochemical recurrence of prostate cancer.
Prognostic or risk stratification purposes linked with tumor stage and Gleason score.
Kits and panels for detecting the biomarkers.
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