Microseminoprotein-Beta Expression in Different Stages of Prostate Cancer.
Microseminoprotein-Beta Expression in Different Stages of Prostate Cancer.
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DOI：
10.1371/journal.pone.0150241
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Visakorpi T
中科院分区：
文献类型：
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作者：
Sjöblom L;Saramäki O;Annala M;Leinonen K;Nättinen J;Tolonen T;Wahlfors T;Nykter M;Bova GS;Schleutker J;Tammela TL;Lilja H;Visakorpi T
微生物蛋白-β（MSMB，MSMB）是由前列腺贡献的丰富的分泌蛋白，并且基于与良性前列腺上皮相比其在癌细胞中的较低表达的观察结果而被认为是前列腺癌（PC）生物标志物。然而，由于目前关于MSMB的文献不一致，我们在一组全面的不同临床阶段的PC中评估了MSMB在蛋白质和mRNA水平上的表达。使用抗MSMB的单克隆和多克隆抗体进行免疫组织化学，以研究代表前列腺切除术的组织标本（n = 261）和接受雄激素剥夺治疗（ADT）的患者的诊断性穿刺活检（n = 100）以及局部复发性去势抵抗性PC（CRPC）（n = 105）和CRPC转移瘤（n = 113）中的蛋白表达。通过qRT-PCR检查前列腺切除术样本中MSMB、核受体共激活因子4（NCOA 4）和MSMB-NCOA 4融合的转录水平，并通过RNA测序检查良性前列腺增生、PC和CRPC样本中的转录水平。我们还测量了369例PC患者和903例对照者的血清MSMB水平，并使用血液DNA对单核苷酸多态性rs 10993994进行了基因分型。MSMB在PC中的表达（29%的切除术和21%的针吸活检）比在CRPC中更频繁（9%的局部复发CRPC和9%的CRPC转移）（p<0.0001）。MSMB蛋白的检测与乳腺癌切除标本的Gleason评分呈负相关（p = 0.024）。在PC中检测到非常低水平的通读MSMB-NCOA 4转录物。血清MSMB水平在PC和对照组中相似，但在校正诊断时的年龄和游离或总PSA水平后，与PC风险显著相关（p<0.001）。PC患者和对照组的血清MSMB水平与rs 10993994基因型显著相关（p<0.0001）。总之，MSMB表达减少与PC的临床进展平行，并且调整的血清MSMB水平与PC风险相关。
Microseminoprotein-beta (MSMB, MSMB) is an abundant secretory protein contributed by the prostate, and is implicated as a prostate cancer (PC) biomarker based on observations of its lower expression in cancerous cells compared with benign prostate epithelium. However, as the current literature on MSMB is inconsistent, we assessed the expression of MSMB at the protein and mRNA levels in a comprehensive set of different clinical stages of PC. Immunohistochemistry using monoclonal and polyclonal antibodies against MSMB was used to study protein expression in tissue specimens representing prostatectomies (n = 261) and in diagnostic needle biopsies from patients treated with androgen deprivation therapy (ADT) (n = 100), and in locally recurrent castration-resistant PC (CRPC) (n = 105) and CRPC metastases (n = 113). The transcript levels of MSMB, nuclear receptor co-activator 4 (NCOA4) and MSMB-NCOA4 fusion were examined by qRT-PCR in prostatectomy samples and by RNA-sequencing in benign prostatic hyperplasia, PC, and CRPC samples. We also measured serum MSMB levels and genotyped the single nucleotide polymorphism rs10993994 using DNA from the blood of 369 PC patients and 903 controls. MSMB expression in PC (29% of prostatectomies and 21% of needle biopsies) was more frequent than in CRPC (9% of locally recurrent CRPCs and 9% of CRPC metastases) (p<0.0001). Detection of MSMB protein was inversely correlated with the Gleason score in prostatectomy specimens (p = 0.024). The read-through MSMB-NCOA4 transcript was detected at very low levels in PC. MSMB levels in serum were similar in cases of PC and controls but were significantly associated with PC risk when adjusted for age at diagnosis and levels of free or total PSA (p<0.001). Serum levels of MSMB in both PC patients and controls were significantly associated with the rs10993994 genotype (p<0.0001). In conclusion, decreased expression of MSMB parallels the clinical progression of PC and adjusted serum MSMB levels are associated with PC risk.