Enzymes of spermine metabolism pathway (ODC, PAO and SMS) showed opposite expression levels, with significantly higher level in HGPIN and PCa tissues [62]. spermine in PCa management. = 15 PCa= 42 healthy controlsPolyamines in 11/15 PCaNR[56]Fair et al., 197512-h/ 24-h urineSpectronic 20 colorimeter= 44 PCa= 13 healthy controlsSimilarly low levels of spermine detected in cancer and healthy controlsNR[57]Sugimoto et al., 1995Morning= 24 urogenital cancer, including 13 PCa= 43 benign urogenital disorders; = 52 healthy controlsDiAcSpm in urogenital cancerNR[58]Hiramatsu et al., 1997Morning= 31 urogenital cancer, including 15 PCa= 42 benign urogenital disorders; = 52 healthy controlsDiAcSpm in urogenital cancer= 66 PCa= 88 BPH, = 11 healthy controlsSpermine in PCa; 0.0001[60]Chiu et al., 2021Pre-biopsy urine with serum PSA level 4C20 ng/mLUPLCCMS/MS= 185 PCa; = 103 HGPCa= 415 healthy controlsSpermine in PCa and HGPCa; 0.001[61]Graaf et al., 2000TissueHPLC= 7 PCa= 4 healthy controls, = 3 BPHSpermine in PCa 0.05[7]Swanson et al., 2003TissueHRMAS= 7 PCa (gland percentage 20) = 13 PCa (gland percentage 20, 8 with GS 6, 5 with GS 7)= 33 healthy controlsSpermine in PCa compared with controls Spermine in PCa with higher GS= 0.01 = 0.05[64]Swanson et al., 2006TissueHRMAS= 60 PCa= 6 healthy controlsSpermine in PCa 0.01[66]Maxeiner et al., 2010TissueHRMAS= 16 PCa with BCR= 32 PCa without BCR (16 clinical-stage-matched and 16 pathological-stage-matched)Spermine alteration predicts PCa recurrenceNR [68]Nagarajan et al., 2010Tissue(2D) J-resolved spectroscopy (JPRESS)= 7 PCa with GS = 4 + 3= 7 PCa with GS = 3 + 4(Cho + Cr)/Spm ratio in PCa with GS = 4 + 3= 0.07[70]Garca-Martn et al., 2011 Tissue1H-MRS= 30= 249Cho/(Cit + Spm) ratio in PCa 0.001[69]Giskeodegar-d et al., 2013TissueHRMAS= 30 PCa with GS = 6;= 81 HGPCa with GS 7= 47 normal adjacent samplesSpermine in PCa and HGPCa compared with normal= 0.022= 0.0044= 2.17 10-4[65]Selnaes et al., 2013TissueIn vivo MRSI and ex vivo HRMAS= 15 PCa with GS 4 + 3 for ex vivo HRMAS= 19 PCa with GS 4 + 3 for in vivo MRSI= 16 PCa with GS 3 + 4 for ex vivo HRMASn = 12 PCa with (GS 3 + 4) for in vivo MRSI(Cho+Spm+Cr/Cit) ratio with increasing GS= 0.035 (ex vivo)= 0.001 (in vivo)[72]Basharat et al., 2015TissueHRMAS= 8 PCa with T3 stage= 19 PCa with GS = 7 = 7 PCa with T1 stage, = 11 with T2 stagen = 6 PCa= 0.04= 0.08= 0.01[67]Hansen et al., 2016TissueHRMAS= 34 ERGhigh PCa= 30 ERGlow PCaSpermine in ERGhigh PCa compared with ERGlow PCa 0.001[75]Shukla-Dave et al., 2016TissueImmunofluo-rescence= 18 HGPIN;= 120 PCa= 103 healthy controlsSpermine in HGPIN and PCa 0.0001[62]Braadland et al., 2017TissueHRMAS= 50 PCa with recurrence= 60 PCa without recurrenceSpermine independently associated with better RFS= 0.016= 0.014[76]Lynch et al., 1997EPS by prostatic massage1H-MRS= 4 PCa= 12 healthy controls; = 10 BPH; = 11 vasal aplasia, = 1 prostatodynia(Cit to Spm) ratio in PCa 0.02[80]Serkova et al., 2008EPS by prostatic massage1H-MRS= 52 PCa= 26 healthy controlsSpermine in PCa 0.002[81]Cipolla et al., 1990Erythrocyte spermineHPLC= 36 PCa with metastases;= 12 PCa with hormonal escape= 17 PCa without metastases;= 41 PCa with hormonal responsivenessSpermine in PCa with metastases 0.01 0.001[83]Cipolla et al., 1993Erythrocyte spermineHPLC= 28 endocrine-treated PCa with progression= 23 endocrine-treated PCa without progressionPretherapeutic spermine level in PCa with progression 0.01[84]Cipolla et al., 1994Erythrocyte spermineHPLC= 40 newly diagnosed, stage D2 PCaNASpermine associated with shorter PFS and CSS in PCaPFS: = 0.001= 0.0025[85]Cipolla et al., 1996Erythrocyte spermineHPLC= 88 PCa with metastasesNAPretherapeutic spermine level predicts worse PFS and CSS in metastatic PCaPFS: 0.0001 0.0005[86] Open in a separate window Abbreviations: NR, not reported; ROC, Receiver operating characteristics; GS, Gleason score; BCR, biochemical recurrence; HGPCa, high-grade prostate cancer; HGPIN, high-grade prostatic intraepithelial neoplasia; RFS: recurrence-free survival; NA, not available; PFS: progression-free survival; CSS: cancer special survival. 4.1. Urine As early as the mid-1970s, Sanford et al. discovered that the excretion of polyamines in the urine of patients harboring PCa was higher than normal individuals [56]. In the same year, Fair et.Human Expressed Prostatic Secretions (EPS) Apart from direct monitoring of prostate tissues, prostatic fluid collected after prostate massage is richer in prostatic metabolites, and is less affected by confounding factors [79]. stress, anticancer immunosurveillance, and apoptosis regulation. Although the specific mechanism of spermine in PCa development is still unclear, ongoing research in spermine metabolism and its association with PCa pathophysiology opens up new opportunities in the diagnostic and therapeutic roles of spermine in PCa management. = 15 PCa= 42 healthy controlsPolyamines in 11/15 PCaNR[56]Fair et al., 197512-h/ 24-h urineSpectronic 20 colorimeter= 44 PCa= 13 healthy controlsSimilarly low levels of spermine detected in cancer and healthy controlsNR[57]Sugimoto et al., 1995Morning= 24 urogenital cancer, including 13 PCa= 43 benign urogenital disorders; = 52 healthy controlsDiAcSpm in urogenital cancerNR[58]Hiramatsu et al., 1997Morning= 31 urogenital cancer, including 15 PCa= 42 benign urogenital disorders; = 52 healthy controlsDiAcSpm in urogenital cancer= 66 PCa= 88 BPH, = 11 healthy controlsSpermine in PCa; 0.0001[60]Chiu et al., Benzydamine HCl 2021Pre-biopsy urine with serum PSA level 4C20 ng/mLUPLCCMS/MS= 185 PCa; = 103 HGPCa= 415 healthy controlsSpermine in PCa and HGPCa; 0.001[61]Graaf et al., 2000TissueHPLC= 7 Rabbit Polyclonal to GLRB PCa= 4 healthy controls, = 3 BPHSpermine in PCa 0.05[7]Swanson et al., 2003TissueHRMAS= 7 PCa (gland percentage 20) = 13 PCa (gland percentage 20, 8 with GS 6, 5 with GS 7)= 33 healthy controlsSpermine in PCa compared with controls Spermine in PCa with higher GS= 0.01 = 0.05[64]Swanson et al., 2006TissueHRMAS= 60 PCa= 6 healthy controlsSpermine in PCa 0.01[66]Maxeiner et al., 2010TissueHRMAS= 16 PCa with BCR= 32 PCa without BCR (16 clinical-stage-matched and 16 pathological-stage-matched)Spermine alteration predicts PCa recurrenceNR [68]Nagarajan et al., 2010Tissue(2D) J-resolved spectroscopy (JPRESS)= 7 PCa with GS = 4 + 3= 7 PCa with GS = 3 + 4(Cho + Cr)/Spm ratio in PCa with GS = 4 + 3= 0.07[70]Garca-Martn et al., 2011 Tissue1H-MRS= 30= 249Cho/(Cit + Spm) ratio in PCa 0.001[69]Giskeodegar-d et al., 2013TissueHRMAS= 30 PCa with GS = 6;= 81 HGPCa with GS 7= 47 normal adjacent samplesSpermine in PCa and HGPCa compared with normal= 0.022= 0.0044= 2.17 10-4[65]Selnaes et al., 2013TissueIn vivo MRSI and ex vivo HRMAS= 15 PCa with GS 4 + 3 for ex vivo HRMAS= 19 PCa with GS 4 + 3 for in vivo MRSI= 16 PCa with GS 3 + 4 for ex vivo HRMASn = 12 PCa with (GS 3 + 4) for Benzydamine HCl in vivo MRSI(Cho+Spm+Cr/Cit) ratio with increasing GS= 0.035 (ex vivo)= 0.001 (in vivo)[72]Basharat et al., 2015TissueHRMAS= 8 PCa with T3 stage= 19 PCa with GS = 7 = 7 PCa with T1 stage, = 11 with T2 stagen = 6 PCa= 0.04= 0.08= 0.01[67]Hansen et al., 2016TissueHRMAS= 34 ERGhigh PCa= 30 ERGlow PCaSpermine in ERGhigh PCa compared with ERGlow PCa 0.001[75]Shukla-Dave et al., 2016TissueImmunofluo-rescence= 18 HGPIN;= 120 PCa= 103 healthy controlsSpermine in HGPIN and PCa 0.0001[62]Braadland et al., 2017TissueHRMAS= 50 PCa with recurrence= 60 PCa without recurrenceSpermine independently associated with better RFS= 0.016= 0.014[76]Lynch et al., 1997EPS by prostatic massage1H-MRS= 4 PCa= 12 healthy controls; = 10 BPH; = 11 vasal aplasia, = 1 prostatodynia(Cit to Spm) ratio in PCa 0.02[80]Serkova et al., 2008EPS by prostatic massage1H-MRS= 52 PCa= 26 healthy controlsSpermine in PCa 0.002[81]Cipolla et al., 1990Erythrocyte spermineHPLC= 36 PCa with metastases;= 12 PCa with hormonal escape= 17 PCa without metastases;= 41 PCa with hormonal responsivenessSpermine in PCa with metastases Benzydamine HCl 0.01 0.001[83]Cipolla et al., 1993Erythrocyte spermineHPLC= 28 endocrine-treated PCa with progression= 23 endocrine-treated PCa without progressionPretherapeutic spermine level in PCa with progression 0.01[84]Cipolla et al., 1994Erythrocyte spermineHPLC= 40 newly diagnosed, stage D2 PCaNASpermine associated with shorter PFS and CSS in PCaPFS: = 0.001= 0.0025[85]Cipolla et al., 1996Erythrocyte spermineHPLC= 88 PCa with metastasesNAPretherapeutic spermine level predicts worse PFS and CSS in metastatic PCaPFS: 0.0001 0.0005[86] Open in a separate window Abbreviations: NR, not reported; ROC, Receiver operating characteristics; GS, Gleason score; BCR, biochemical recurrence; HGPCa, high-grade prostate.