A peak at m/z 10,760 was identified as β-microseminoprotein (β-MSMB) and found to be statistically lower in urine from PCa participants using the peak's average areas.
Across 66 meta-analyses, a total of 20 genetic variants involving 584,100 subjects in 19 different genes (KLK3, IGFBP3, ESR1, SOD2, CAT, CYP1B1, VDR, RFX6, HNF1B, SRD5A2, FGFR4, LEP, HOXB13, FAS, FOXP4, SLC22A3, LMTK2, EHBP1 and MSMB) exhibited significant association with prostate cancer.
rs10993994 in MSMB promoter affects serum MSMB expression, contributes to the genetic predisposition to prostate cancer in southern Chinese Han population.
Quantitative RT-PCR analysis revealed that MSMB, NBL1 and AZGP1 were expressed with much higher specificity in PCa and NP than in 14 other kinds of normal tissue.
Variants in the promoter of the MSMB gene have been associated with the risk of prostate cancer (PCa) in several independent genome-wide association studies.
SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease.
A plausible functional basis for a few loci, such as FGFR2 for breast cancer and MSMB for prostate cancer, has been elucidated, but the majority are not understood and suggest new mechanisms of carcinogenesis.
Further improvement was achieved by multivariate logistic regression analysis, which identified novel duplex (TRPM8 and MSMB), triplex (plus AMACR) and quadriplex (plus PCA3) models for the detection of early CaPs (AUC=0.665, 0.726 and 0.741, respectively).
Of note, rs7000448 is in strong linkage disequilibrium with rs10761581 in NCOA4, a SNP that has been implicated to be independently associated, with respect to the widely reported SNP rs10993994 in the nearby gene MSMB, with prostate cancer in men of European descent.
Independent investigators have previously identified differential expression of two of these three genes, hepsin and beta-microseminoprotein, in prostate cancer.
Additional copies of the prostate cancer risk allele resulted in lower beta-MSP but higher PSA levels, and singly explained 23% and 5% of the variation seen in semen beta-MSP and PSA, respectively.
Methylation-specific polymerase chain reaction (MSP) targeting promoter hypermethylation of the glutathione S transferase P1 gene (GSTP1), as the most frequent DNA alteration in prostatic carcinoma, was used for the molecular detection of cell-bound and cell-free prostate tumor DNA in various human bodily fluids.
Recent functional work has shown that different alleles of the significantly associated SNP in the promoter of MSMB found to be associated with prostate cancer risk, rs10993994, can influence its expression in tumors and in vitro studies.
These data indicate that the increase in PC risk associated with rs10993994:C>T is likely mediated by the variant's effect on PSP94 expression; however, this effect does not extend to NCOA4 in the data presented here.
We also review the diagnostic assays that are developed for PSP94 for use in the diagnosis of PCa and use of such tests in the differential diagnosis of PCa from benign prostatic hyperplasia (BPH).
We assessed the performance of a 4-kallikrein panel with and without microseminoprotein-β to predict high grade (Gleason 7+/Gleason Grade Group 2+) prostate cancer on biopsy in a multiethnic cohort from PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial).