1000/1000
Hot
Most Recent
Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers.
Advantages |
Critical Issues |
Availability |
Potential Clinical Utility |
---|---|---|---|
Serum Biomarkers: PHI, 4K scores |
|||
Easy to perform Reproducible |
High risk of confounding factors Include PSA for interpretation Include clinical variables (4Kscore) Uncertain reference range and ethnic variability (PHI) |
PHI: FDA-approved 4K: CLIA-certified |
Primary Diagnosis (biopsy-naïve/repeat biopsy) Diagnosis of csPC AS |
Urinary Biomarkers: PCA3, SelectMDx, MiPS, ExoDx |
|||
Easy to collect Large quantities Reproducible Fewer confounding elements |
Need DRE (not ExoDx) Visit to a health-care provider to obtain the urine sample (not ExoDx) Difficult to collect cells derived from PC Include clinical variables (SelectMDx) Uncertain cut-off value (PCA3) |
PCA3: FDA-Approved SelecMDx, MiPS, and ExoDx: CLIA-certified |
Primary Diagnosis (biopsy-naïve/repeat biopsy) Diagnosis of csPC AS |
Biomarkers |
Primary Diagnosis of PC (No. of pts, Inclusion Criteria, AUC Results) |
Primary Diagnosis Repeat Biopsy (No. of pts, Inclusion Criteria, AUC Results) |
Diagnosis of csPC (No. of pts, Inclusion Criteria, AUC Results) |
Active Surveillance (No. of pts, Inclusion Criteria, AUC Results) |
---|---|---|---|---|
Serum |
||||
PHI |
No. pts 892 |
No. pts 95 |
No. pts 658 |
No. pts 253 |
PSA 2–10 ng/mL |
AUC 0.72 [35] |
PSA 4–10 ng/mL |
AUC 0.65 for GR [36] |
|
AUC 0.72 [31] |
AUC 0.71 [37] |
|||
No. pts 658 |
No. pts 391 |
No. pts 769 |
||
PSA 4–10 ng/mL |
PSA 2–10 ng/mL |
PSA 2–10 ng/mL |
||
AUC 0.71 [37] |
AUC 0.78 [38] |
AUC 0.72 all (0.68 initial biopsy, 0.78 repeat biopsy) [38] |
||
No. pts 300 |
No. pts 110 |
|||
PSA 2–10 ng/mL |
PSA 2–20 ng/mL |
|||
AUC 0.77 [39] |
AUC 0.69 [40] |
|||
4K Score |
No. pts 749 |
No. pts 925 |
No. pts 749 |
No. pts 718 |
PSA > 3 ng/mL |
PSA > 3 ng/mL |
PSA > 3 ng/mL |
AUC 0.78 for GR [41] |
|
AUC 0.69 including age and DRE [42] |
AUC 0.68 including age, PSA, DRE [43] |
AUC 0.78 including age and DRE [42] |
||
No. pts 531 |
No. pts 531 |
|||
PSA 3–15 ng/mL |
PSA 3–15 ng/mL |
|||
AUC 0.69 including age [34] |
AUC 0.71 including age [34] |
|||
No. pts 740 |
No. pts 740 |
|||
PSA > 3 ng/mL |
PSA > 3 ng/mL |
|||
AUC 0.83 including age, PSA, DRE [44] |
AUC 0.90 including age, PSA, DRE [44] |
|||
No. pts 925 |
||||
PSA > 3 ng/mL |
||||
AUC 0.87 including age, PSA, DRE [43] |
||||
Urinary |
||||
PCA3 |
No. pts 300 |
No. pts 48 |
No. pts 497 |
No. pts 552 |
PSA 2–10 ng/mL |
PSA 2.5–6.5 ng/mL |
PSA > 3 ng/mL |
AUC for GR 0.61 [45] |
|
AUC 0.73 [39] |
AUC 0.79 [46] |
AUC 0.53 [47] |
||
No. pts 497 |
No. pts 470 |
No. pts 905 |
No. pts 294 |
|
PSA > 3 ng/mL |
Any PSA |
PSA > 3 ng/mL |
AUC for GR 0.58 [48] |
|
AUC 0.72 [47] |
AUC 0.65 [49] |
AUC 0.65 [25] |
||
No. pts 578 PSA <50 ng/mL AUC 0.75, PSA 4–10 ng/mL, AUC 0.74 [50] |
No. pts 103 Any PSA AUC 0.64 [51] |
No. pts 138 PSA 4–20 ng/mL AUC 0.55 [52] |
||
SelectMDx |
No. pts 52 |
No. pts 114 |
No. pts 125 |
|
PSA > 3 ng/mL |
PSA > 3 ng/mL |
AUC for GR 0.70 [53] |
||
AUC 0.92 [54] |
AUC 0.67 [55] |
|||
No. pts 905 |
||||
PSA > 3 ng/mL |
||||
AUC 0.76 [25] |
||||
MiPS |
No. pts 1225 |
No. pts 1225 |
||
PSA > 3 ng/mL |
PSA > 3 ng/mL |
|||
AUC 0.75 [26] |
AUC 0.7 [26] |
|||
ExoDX |
No. pts 195 |
No. pts 195 |
||
PSA 2–10 ng/mL |
PSA 2–10 ng/mL |
|||
AUC 0.73 [27] |
AUC 0.80 [27] |
|||
No. pts 519 |
||||
PSA 2–10 ng/mL |
||||
AUC 0.73 [28] |
Source |
Experimental Approach |
Sample Cohort |
Main Findings |
Ref |
---|---|---|---|---|
Tissue |
HR-MAS combined with multivariate analysis (PLS, PLS–DA) and absolute quantification (LCModel) |
no. pts = 48 |
Low levels of spermine and citrate are correlated with PC aggressiveness. |
[76] |
Prostatic fluid |
1H NMR spectroscopy coupled to multiple regression analysis |
no. pts = 38 |
Significance differences between citrate and spermine ratio in PC. |
[77] |
Serum |
1H NMR spectroscopy coupled to multivariate analysis |
no. pts = 210 |
Glycine, sarcosine, alanine, creatine, xanthine, and hypoxanthine were able to determine abnormal prostate (BPH + PC). |
[78] |
Tissue, urine, and plasma |
UHPLC-MS and GC–MS |
no. pts = 110 |
Sarcosine and N-methyl derivative of glycine were highly elevated during PC progression to metastasis. |
[79] |
Tissue |
1H HR-MAS spectroscopy |
no. pts = 20 |
High choline and phosphocholine levels, along with an increase in the glycolytic products lactate and alanine in PC. |
[80] |
Urine |
UHPLC-MS/MS coupled to ROC curve analysis |
no. pts = 148 |
Kynurenic acid was found a promising biomarker for PC detection. Sarcosine was not found as significant biomarker for the diagnosis of PC. |
[81] |
Serum and urine |
LC–ESI–MS/MS technique and the aTRAQ reagent couple to ROC and multivariate (PLS–DA) analyses |
no. pts = 89 |
Ethanolamine, arginine markers for PC. |
[82] |
Urine |
ID GC/MS couple to PCA and ROC analyses |
no. pts = 48 |
Sarcosine has no statistical difference between the PC group and in the non-PC group. Decreased urinary levels of glycine, threonine, and alanine was observed in PC group. |
[83] |
Urine |
HPLC–TOF/MS in positive and negative polarity as well as GC–QqQ/MS couple to PCA and PLS–DA analyses |
no. pts = 64 |
Altered levels of urinary metabolites involved in such biochemical pathways like AA, purine and glucose metabolism as well as urea and TCA cycle may be considered as potential markers of PC. |
[84] |
Serum |
LC–MS and GC–MS |
no. pts = 400 |
PC risk was correlated with the levels of α-ketoglutarate, thyroxine, TMAO, and erucoyl-sphingomyelin; metabolites involved in the metabolism of nucleotides, steroid hormones, and tobacco were associated with non-aggressive PC. |
[85] |
Abbreviations list: Ref = reference; no. pts = number of patients; PC = prostate cancer; pts = patients; HR-MAS = high resolution magic angle spinning MRS; UHPLC-MS = high throughput liquid mass spectrometry; GC–MS = gas chromatography-based mass spectrometry; NMR = nuclear magnetic resonance; ROC = receiving operating characteristics; PLS–DA = partial least squares–discriminant analysis; PCA = principal component analysis; ID GC/MS = isotope dilution gas chromatography/mass spectrometry; HPLC–TOF/M = high performance liquid chromatography coupled with time of flight mass spectrometry; GC–QqQ/MS = gas chromatography coupled with triple quadruple mass spectrometry; BPH = benign prostate hypertrophy; RP = radical prostatectomy; PSA = prostate-specific antigen; US = ultra-sound; TMAO = trimethylamine oxide; TCA = tricarboxylic acid.
Exosomal Biomarkers |
Source |
Isolation Method |
Potential Use |
Ref |
---|---|---|---|---|
PSA |
Plasma |
UC |
Screening/Early Diagnosis |
|
CA IX |
Plasma |
UC |
Diagnosis |
[104] |
Survivin |
Plasma |
UC |
Early Diagnosis |
[107] |
Exosomes levels |
Plasma |
UC |
Diagnosis/Prognosis/Disease surveillance |
[108] |
PTEN |
Plasma |
UC |
Diagnosis |
[109] |
miR-141, miR-375 |
Serum |
FCE |
Diagnosis/Stage Determination |
[110] |
miR-1290, miR-375 |
Plasma |
PP |
Prognosis |
[111] |
miR-141 |
Serum |
PP |
Diagnosis |
[112] |