和基因型与良性前列腺增生和前列腺癌中 PSA 水平和免疫表型的相关性。

Associations of and Genotypes with PSA Levels and Immunophenotype in Benign Prostatic Hyperplasia and Prostate Cancer.

机构信息

Oncology Center, 103 Military Hospital, Vietnam Military Medical University, Ha Dong, 151530 Hanoi, Vietnam.

Radiology Center, 103 Military Hospital, Vietnam Military Medical University, Ha Dong, 151530 Hanoi, Vietnam.

出版信息

Front Biosci (Landmark Ed). 2024 Jul 19;29(7):256. doi: 10.31083/j.fbl2907256.

DOI:10.31083/j.fbl2907256

PMID:39082359

Abstract

BACKGROUND

Prostate cancer (PCa) is one of the most common malignant tumors of the male urinary system, and its incidence and mortality rates have been increasing worldwide. Benign prostatic hyperplasia (BPH) represents stromal and epithelial cell proliferation in the prostate in elderly males. Abnormal activation of inflammation-related signalling molecules, such as toll-like receptor 4 (TLR4) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) has been linked to the initiation and progression of various human diseases including PCa and BPH. Cylindromatosis gene alterations are associated with PCa progression. In this study, the contribution of , , and gene variants to PCa and BPH risks and their associations with prostate-specific antigen (PSA) levels, immunophenotype, and clinical features in Vietnamese men were determined.

METHODS

A total of 102 patients with PCa, 65 with BPH, and 114 healthy controls were enrolled. The immunophenotype was analyzed by flow cytometry, cytokine secretion by enzyme-linked immunosorbent assay (ELISA), and gene variants by DNA sequencing.

RESULTS

Lower levels of transforming growth factor β (TGF-β) and higher numbers of CD13+CD117- and CD56+CD25+ cells were observed in the PCa group than in the BPH group. Genetic analysis of the gene identified five single nucleotide polymorphisms (SNPs), of which c.2351-47 C>T, c.2351-46A>T, and rs1971432171 T>G had significantly higher frequencies in PCa patients than in the control and BPH groups. Sequencing of the gene revealed five nucleotide changes, in which the rs2149356 SNP showed an increased risk for both PCa and BPH and the c.331-206 SNP had a reduced risk for PCa. Importantly, the expansion of activated natural killer (NK) cells and higher levels of PSA were found in PCa patients carrying the CT genotype of the c.2351-47 compared to those with the wild-type genotype.

CONCLUSION

Activation of NK cells in -sensitive PCa patients was associated with serum PSA release and the CYLD c.2351-47 variant may be a significant risk factor for prostatitis in PCa patients.

摘要

背景

前列腺癌（PCa）是男性泌尿系统中最常见的恶性肿瘤之一，其发病率和死亡率在全球范围内呈上升趋势。良性前列腺增生（BPH）是老年男性前列腺中基质和上皮细胞的增殖。炎症相关信号分子（如 toll 样受体 4（TLR4）和 Janus 激酶/信号转导和转录激活因子（JAK/STAT））的异常激活与包括 PCa 和 BPH 在内的各种人类疾病的发生和发展有关。Cylindromatosis 基因改变与 PCa 的进展有关。在这项研究中，确定了、和基因变异与 PCa 和 BPH 风险的关系，并确定了它们与越南男性前列腺特异性抗原（PSA）水平、免疫表型和临床特征的关系。

方法

共纳入 102 例 PCa 患者、65 例 BPH 患者和 114 例健康对照者。通过流式细胞术分析免疫表型，通过酶联免疫吸附试验（ELISA）分析细胞因子分泌，通过 DNA 测序分析基因变异。

结果

与 BPH 组相比，PCa 组 TGF-β水平较低，CD13+CD117-和 CD56+CD25+细胞数量较多。基因分析发现基因有 5 个单核苷酸多态性（SNPs），其中 c.2351-47 C>T、c.2351-46A>T 和 rs1971432171 T>G 在 PCa 患者中的频率明显高于对照组和 BPH 组。基因测序发现 5 个核苷酸变化，其中 rs2149356 SNP 增加了 PCa 和 BPH 的风险，c.331-206 SNP 降低了 PCa 的风险。重要的是，与野生型基因型相比，携带基因 c.2351-47 CT 基因型的 PCa 患者中 NK 细胞的激活和 PSA 水平升高。