Study On The Clinically Relevant Inflammatory Indicators And Proteomics In Patients With Benign Prostatic Hyperplasia

Objective:1 To investigate the relationship between histological inflammation and indicators of systemic inflammation in patients with benign prostatic hyperplasia(BPH).2 Differentially expressed proteins were screened in BPH tissue specimens with different degrees of histological inflammation using proteomics technology.It provides new clues for finding the molecular basis of the occurrence and development of BPH,and finds new potential targets for the prevention and treatment of BPH.Methods:1 The clinical information of 248 patients who underwent transurethral resection of the prostate(TURP)was collected.Based on the tissue samples’hematoxylin-eosin staining results,the patients were divided into four groups.The levels of systemic immune inflammation index(SII),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),lymphocyte to monocyte ratio(LMR),and platelet to albumin ratio(PAR)were compared between the groups,SPSS software(v.26.0)was used for statistics.2 Based on the results of HE staining,three tissue specimens from the Mild BPH group,Mod_BPH group and Sev BPH group were randomly selected respectively.The proteins were extracted from the specimens,digested by trypsin,and quantitatively analyzed by liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins in the BPH groups with different histological inflammation.The differentially expressed proteins were then subjected to bioinformatics analysis such as functional annotation,GO analysis,KEGG enrichment,and expression pattern clustering.Results:1 Among the 248 patients with BPH,43 cases(17.3%)were in the BPH alone group(BPH),and 205(82.7%)were in the BPH combined with histological inflammation group.Whereas in the combined histological inflammation group,91 cases(44.4%)were in the combined mild histological inflammation group(Mild_BPH),79 cases(38.5%)were in the combined moderate histological inflammation group(Mod_BPH),and 35 cases(17.1%)were in the combined severe histological inflammation group(Sev_BPH).2 The differences in SII and NLR between the BPH alone group and the combined histological inflammation BPH group were statistically significant(P<0.05).And the differences in SII and NLR were also statistically significant(P<0.05)in the BPH alone group compared with the BPH combined with different histological inflammation groups(Mild BPH group,Mod_BPH group,and Sev_BPH group),respectively.In contrast,PLR,LMR,and PAR were not statistically different in any of the above cases P>0.05).3 Between the groups with BPH combined with different histological inflammation,SII and NLR increased with increasing inflammation,and the difference was statistically significant(P<0.05).PLR,LMR,and PAR were not statistically different between the groups(P>0.05).Meanwhile,our further analysis revealed that prostate volume(PV)was positively correlated with SII.4 The results of proteomic study showed that a total of 5258 proteins were detected from each BPH combined histological inflammation group.A total of 144 differentially expressed proteins were identified,using 1.5-fold differential expression as the criterion for significant upregulation and significant downregulation(P<0.05).These differentially expressed proteins were mainly associated with pentose phosphate pathway,PPAR signaling pathway,fatty acid synthesis and degradation,glycerophospholipid metabolism,and adipokine signaling pathway.Among them,there were 53 differentially expressed proteins in the Mod_BPH vs Mild_BPH comparison group and 100 differentially expressed proteins in the Sev_BPH vs Mild_BPH comparison group.5 By further analysis,we jointly screened nine differential overlapping proteins in the Sev_BPH vs Mild_BPH and Mod_BPH vs Mild_BPH comparison groups.Among them,acyl-protein thioesterase 1(LYPLA1),carnitine O-palmitoyltransferase 1(CPT1A),solute carrier family 12 member 2(SLC12A2),thiosulfate:glutathione sulfurtransferase(TSTD1),STE20/SPS1-related proline-alanine-rich protein kinase(STK3 9)protein was up-regulated in both comparison groups.Phospholipid phosphatase 3(PPAP2B),hyaluronan and proteoglycan link protein 1(HAPLN1),prohibitin-2(PHB2),and deoxyribose-phosphate aldolase(DERA)were down-regulated in both comparison groups.6 Biological information analysis showed that these differential proteins were significantly different in nucleus,cytoplasm,extracellular and mitochondria.The main molecular functions are catalytic and binding activities,and they are related to catalytic,binding and transporter activities.In addition,protein-protein interaction network analysis showed that the nine trend differential proteins obtained were all related to other proteins.Among them,CPT1 A,DERA and PHB2 had closer interactions with other proteins.Conclusion:1 BPH patients with combined histological inflammation had higher SII and NLR,and SII and NLR tended to increase with increasing inflammation;PV was positively correlated with SII.2 9 differential proteins,including CPT1A,DERA,PHB2,PPAP2B,STK39,SLC12A2,LYPLA1,TSTD1,and HAPLN1,were identified from BPH tissues with different degrees of combined histological inflammation,which may promote the progression of BPH combined with histological inflammation.3 Among them,CPT1A,PHB2 and DERA are closely associated with other proteins.CPT1A,PHB2 are involved in lipid metabolism,mitochondrial autophagy and other energy metabolism related pathways pathways are closely related to histological inflammation.