METHODS FOR DIFFERENTIATING BENIGN PROSTATIC HYPERPLASIA FROM PROSTATE CANCER
Methods for differentiating between benign prostatic hyperplasia (BPH) and prostate cancer, in a subject, are provided, such methods including the detection of levels of one or more biomarker diagnostic of BPH. The invention also provides a kit for the diagnosis of BPH, without the need for a biopsy.
1 . A method for differentiating benign prostatic hyperplasia (BPH) from prostate cancer, comprising:
(a) detecting the protein level of Filamin A (FLNA) in a biological sample from the subject;
(b) measuring the prostate volume of the subject;
(c) analyzing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample with a corresponding predetermined threshold value for FLNA level, age and prostate volume; and
(d) determining whether the subject has BPH or prostate cancer by comparing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample to the corresponding threshold value.
2 . The method of claim 1 , wherein if the protein level of FLNA, prostate volume, and age of the subject is below the corresponding predetermined threshold value, the subject is diagnosed with BPH, and if the protein level of FLNA, prostate volume, and age of the subject is above the corresponding predetermined threshold value, the subject is diagnosed with prostate cancer.
3 . The method of claim 1 , wherein the protein level of FLNA is detected using an assay selected from an immunoassay, an enzyme-linked immunosorbent assay (ELISA), immunoprecipitation multiple reaction monitoring (IP-MRM), or a mass spectrometry assay.
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7 . The method of claim 1 , wherein the biological sample is selected from the group consisting of blood, serum, plasma, and urine.
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9 . The method of claim 1 , wherein the age of the subject is 50 years or older, the subject is experiencing lower urinary tract symptoms (LUTS), the subject has an enlarged prostate gland as determined by digital rectal examination (DRE), and/or the subject has an elevated prostate specific antigen (PSA) level.
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12 . The method of claim 1 , wherein the subject does not have an enlarged prostate gland as determined by digital rectal examination (DRE).
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15 . The method of claim 1 , wherein the subject has had one or more prostate biopsies.
16 . The method of claim 1 , wherein the BPH is differentiated from prostate cancer in a subject having an intermediate Gleason score of from 5 to 7 or a high Gleason score of greater than 8.
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18 . The method of claim 1 , further comprising administering to the subject diagnosed with BPH a therapeutic treatment for BPH.
19 . The method of claim 18 , wherein the therapeutic treatment comprises a selective α 1 -blocker, a 5α-reductase inhibitor, an antimuscarinic, a phosphodiesterase-5 inhibitor, a surgery, a prostatic stent, a high intensity focused ultrasound, an interstitial laser coagulation, a transurethral electroevaporation of the prostate, a transurethral microwave thermotherapy, a transurethral needle ablation, a photoselective vaporization, or a combination thereof.
20 . A method for diagnosing benign prostatic hyperplasia (BPH) in a subject, comprising:
(a) detecting the protein level of Filamin A (FLNA) in a biological sample from the subject;
(b) measuring the prostate volume of the subject;
(c) analyzing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample with a corresponding predetermined threshold value for FLNA level, age and prostate volume; and
(d) determining whether the subject has BPH by comparing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample to the corresponding threshold value.
21 . The method of claim 20 , wherein if the protein level of FLNA, prostate volume, and age of the subject are below the corresponding predetermined threshold value, the subject is diagnosed with BPH.
22 . The method of claim 20 , wherein the protein level of FLNA is detected using an assay selected from an immunoassay, an enzyme-linked immunosorbent assay (ELISA), immunoprecipitation multiple reaction monitoring (IP-MRM), or a mass spectrometry assay.
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26 . The method of claim 20 , wherein the biological sample is selected from the group consisting of blood, serum, plasma, and urine.
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28 . The method of claim 20 , wherein the age of the subject is 50 years or older, the subject is experiencing lower urinary tract symptoms (LUTS), the subject has an enlarged prostate gland as determined by digital rectal examination (DRE), and/or the subject has an elevated prostate specific antigen (PSA) level.
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31 . The method of claim 20 , wherein the subject does not have an enlarged prostate gland as determined by digital rectal examination (DRE).
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34 . The method of claim 20 , wherein the subject has had one or more prostate biopsies.
35 . The method of claim 20 , further comprising administering to the subject a therapeutic treatment for BPH.
36 . The method of claim 35 , wherein the therapeutic treatment comprises a selective α 1 -blocker, a 5α-reductase inhibitor, an antimuscarinic, a phosphodiesterase-5 inhibitor, a surgery, a prostatic stent, a high intensity focused ultrasound, an interstitial laser coagulation, a transurethral electroevaporation of the prostate, a transurethral microwave thermotherapy, a transurethral needle ablation, a photoselective vaporization, or a combination thereof.
37 . A method for treating BPH comprising:
(a) detecting the protein level of Filamin A (FLNA) in a biological sample from the subject;
(b) measuring the prostate volume of the subject;
(c) analyzing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample with a corresponding predetermined threshold value for FLNA level, age and prostate volume; and
(d) determining whether the subject has BPH or prostate cancer by comparing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample to the corresponding threshold value,
wherein if the subject has BPH, the subject is administered a treatment comprising a selective α 1 -blocker, a 5α-reductase inhibitor, an antimuscarinic, a phosphodiesterase-5 inhibitor, a surgery, a prostatic stent, a high intensity focused ultrasound, an interstitial laser coagulation, a transurethral electroevaporation of the prostate, a transurethral microwave thermotherapy, a transurethral needle ablation, a photo selective vaporization, or a combination thereof.
38 . The method of claim 37 , wherein the subject is not subjected to a prostate biopsy.
39 . The method of claim 37 , wherein the protein level of FLNA is detected using an assay selected from an immunoassay, an enzyme-linked immunosorbent assay (ELISA), immunoprecipitation multiple reaction monitoring (IP-MRM), or a mass spectrometry assay.
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43 . The method of claim 37 , wherein the biological sample is selected from the group consisting of blood, serum, plasma, and urine.
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45 . The method of claim 37 , wherein the age of the subject is 50 years or older, the subject is experiencing lower urinary tract symptoms (LUTS), the subject has an enlarged prostate gland as determined by digital rectal examination (DRE), and/or the subject has an elevated prostate specific antigen (PSA) level.
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51 . A method for avoiding an unnecessary prostate biopsy in a subject, comprising:
(a) detecting the protein level of Filamin A (FLNA) in a biological sample from the subject;
(b) measuring the prostate volume of the subject;
(c) analyzing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample with a corresponding predetermined threshold value for FLNA level, age and prostate volume; and
(d) determining whether the subject has BPH or prostate cancer by comparing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample to the corresponding threshold value, wherein a biopsy is not required if the subject has BPH.
52 . The method of claim 51 , wherein if the protein level of FLNA, prostate volume, and age of the subject is below the corresponding predetermined threshold value, the subject does not require a prostate biopsy.
53 . The method of claim 51 , wherein the protein level of FLNA is detected using an assay selected from an immunoassay, an enzyme-linked immunosorbent assay (ELISA), immunoprecipitation multiple reaction monitoring (IP-MRM), or a mass spectrometry assay.
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59 . The method of claim 51 , wherein the age of the subject is 50 years or older, the subject is experiencing lower urinary tract symptoms (LUTS), the subject has an enlarged prostate gland as determined by digital rectal examination (DRE), and/or the subject has an elevated prostate specific antigen (PSA) level.
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62 . The method of claim 51 , wherein the subject does not have an enlarged prostate gland as determined by digital rectal examination (DRE).
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65 . The method of claim 51 , wherein the subject has had one or more prostate biopsies.
66 . A method for monitoring a subject suspected of having benign prostate hyperplasia (BPH) or prostate cancer, comprising:
(a) detecting the protein level of Filamin A (FLNA) in a biological sample from the subject;
(b) measuring the prostate volume of the subject;
(c) analyzing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample with a corresponding predetermined threshold value for FLNA level, age and prostate volume; and
(d) monitoring whether the subject has BPH or prostate cancer by comparing the age of the subject, the prostate volume of the subject, and the protein level of FLNA in the biological sample to the corresponding threshold value.
67 . The method of claim 66 , wherein if the protein level of FLNA, prostate volume, and age of the subject is below the corresponding predetermined threshold value, the subject is diagnosed with BPH, and if the protein level of FLNA, prostate volume, and age of the subject is above the corresponding predetermined threshold value, the subject is diagnosed with prostate cancer.
68 . The method of claim 66 , wherein the monitoring is performed more than once.
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83 . A kit for differentiating benign prostatic hyperplasia (BPH) from prostate cancer in a subject comprising one or more reagents for detecting a level of FLNA in a biological sample and a set of instructions for detecting the level of FLNA in the biological sample, and for differentiating BPH from prostate cancer by analyzing the level of FLNA in the biological sample, the prostate volume of the subject, and the age of the subject.
84 . The kit of claim 83 , wherein the biological sample is obtained from a subject having, suspected of having, or at risk for having a prostate condition.
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86 . The kit of claim 83 , wherein the age of the subject is 50 years or older, the subject is experiencing lower urinary tract symptoms (LUTS), the subject has an elevated prostate specific antigen (PSA) level, and/or the subject has an enlarged prostate gland as determined by digital rectal examination (DRE).
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94 . The kit of claim 83 , wherein the instructions comprise a predetermined threshold value of FLNA level for comparing to the FLNA level in the biological sample from the subject.
95 . The kit of claim 83 , wherein the instructions comprise directions for performing an immunoassay, ELISA, immunoprecipitation multiple reaction monitoring (IP-MRM), or mass spectrometry assay for detecting the level of FLNA in the biological sample.
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